dbSNP rs144001285: PCCB:c.1499-48A>G (chr3-136329857-A-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000532.5(PCCB):c.1499-48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,610,844 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 15 hom. )

Consequence

PCCB
NM_000532.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.908

Publications

0 publications found

Variant links:

Genes affected

PCCB (HGNC:8654): (propionyl-CoA carboxylase subunit beta) The protein encoded by this gene is a subunit of the propionyl-CoA carboxylase (PCC) enzyme, which is involved in the catabolism of propionyl-CoA. PCC is a mitochondrial enzyme that probably acts as a dodecamer of six alpha subunits and six beta subunits. This gene encodes the beta subunit of PCC. Defects in this gene are a cause of propionic acidemia type II (PA-2). Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

PCCB Gene-Disease associations (from GenCC):

propionic acidemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Myriad Women’s Health, Orphanet

PCCB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-136329857-A-G is Benign according to our data. Variant chr3-136329857-A-G is described in ClinVar as Benign. ClinVar VariationId is 256373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCCB	NM_000532.5 link	c.1499-48A>G		intron_variant	Intron 14 of 14	ENST00000251654.9	NP_000523.2	P05166-1
PCCB	NM_001178014.2 link	c.1559-48A>G		intron_variant	Intron 15 of 15		NP_001171485.1	P05166-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCB	ENST00000251654.9 link	c.1499-48A>G		intron_variant	Intron 14 of 14	1	NM_000532.5	ENSP00000251654.4		P05166-1

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

353

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00350

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00225

AC:

564

AN:

250130

AF XY:

0.00227

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00283

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000463

Gnomad NFE exome

AF:

0.00347

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00357

AC:

5210

AN:

1458602

Hom.:

Cov.:

AF XY:

0.00347

AC XY:

2521

AN XY:

725848

show subpopulations

African (AFR)

AF:

0.000748

AC:

AN:

33408

American (AMR)

AF:

0.00318

AC:

142

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.000268

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.000859

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.000356

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.000524

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00427

AC:

4732

AN:

1109310

Other (OTH)

AF:

0.00345

AC:

208

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

280

560

841

1121

1401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

376

564

752

940

<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:

0.00232

AC:

353

AN:

152242

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.000698

AC:

AN:

41548

American (AMR)

AF:

0.00445

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000623

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00350

AC:

238

AN:

68016

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00256

Hom.:

Bravo

AF:

0.00258

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.12

(source)

DANN

Benign

0.67

PhyloP100

-0.91

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over