rs7122539

Variant names:

• chr11-66895260-G-A
• rs7122539
• NM_001040716.2:c.1-23101C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-66895260-G-A
• chr11-66895260-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040716.2(PC):​c.1-23101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,796 control chromosomes in the GnomAD database, including 14,591 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (14591 hom., cov: 30)
• Consequence: PC NM_001040716.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 41 publications found

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: G2P, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040716.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PC	NM_001040716.2	MANE Select	c.1-23101C>T		intron	N/A	NP_001035806.1	P11498-1
	PC	NM_000920.4		c.1-23101C>T		intron	N/A	NP_000911.2	P11498-1
	PC	NM_001439352.1		c.1-23101C>T		intron	N/A	NP_001426281.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PC	ENST00000393960.7	TSL:5 MANE Select	c.1-23101C>T		intron	N/A	ENSP00000377532.1	P11498-1
	PC	ENST00000393955.6	TSL:1	c.-1+12561C>T		intron	N/A	ENSP00000377527.2	P11498-1
	PC	ENST00000393958.7	TSL:1	c.1-23101C>T		intron	N/A	ENSP00000377530.2	P11498-1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63706 AN: 151678 Hom.: 14542 Cov.: 30

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.400

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.420 AC: 63805 AN: 151796 Hom.: 14591 Cov.: 30 AF XY: 0.420 AC XY: 31128 AN XY: 74186

African (AFR) AF: 0.609 AC: 25187 AN: 41348

American (AMR) AF: 0.324 AC: 4950 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1235 AN: 3472

East Asian (EAS) AF: 0.466 AC: 2406 AN: 5158

South Asian (SAS) AF: 0.271 AC: 1305 AN: 4812

European-Finnish (FIN) AF: 0.425 AC: 4473 AN: 10518

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 22995 AN: 67916

Other (OTH) AF: 0.398 AC: 838 AN: 2104

Alfa AF: 0.366 Hom.: 38527

Bravo AF: 0.424

Asia WGS AF: 0.419 AC: 1460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.83
DANN	Benign	0.63
PhyloP100		-0.088
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7122539; hg19: chr11-66662731;