NM_001040716.2:c.3462G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001040716.2(PC):c.3462G>A(p.Glu1154Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PC
NM_001040716.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.118

Publications

0 publications found

Variant links:

Genes affected

PC (HGNC:8636): (pyruvate carboxylase) This gene encodes pyruvate carboxylase, which requires biotin and ATP to catalyse the carboxylation of pyruvate to oxaloacetate. The active enzyme is a homotetramer arranged in a tetrahedron which is located exclusively in the mitochondrial matrix. Pyruvate carboxylase is involved in gluconeogenesis, lipogenesis, insulin secretion and synthesis of the neurotransmitter glutamate. Mutations in this gene have been associated with pyruvate carboxylase deficiency. Alternatively spliced transcript variants with different 5' UTRs, but encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

PC Gene-Disease associations (from GenCC):

pyruvate carboxylase deficiency disease
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P
pyruvate carboxylase deficiency, benign type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
pyruvate carboxylase deficiency, infantile form
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
pyruvate carboxylase deficiency, severe neonatal type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 11-66848974-C-T is Benign according to our data. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-66848974-C-T is described in CliVar as Likely_benign. Clinvar id is 2159533.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.118 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PC	NM_001040716.2 link	c.3462G>A	p.Glu1154Glu	synonymous_variant	Exon 23 of 23	ENST00000393960.7	NP_001035806.1	P11498-1A0A024R5C5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PC	ENST00000393960.7 link	c.3462G>A	p.Glu1154Glu	synonymous_variant	Exon 23 of 23	5	NM_001040716.2	ENSP00000377532.1		P11498-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251258

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112010

Other (OTH)

AF:

0.0000662

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Pyruvate carboxylase deficiency

Benign:1

Apr 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.7

(source)

DANN

Benign

0.82

PhyloP100

-0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over