Variant 13-100089137-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000282.4(PCCA):c.17T>C(p.Val6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PCCA
NM_000282.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.299

Variant links:

Genes affected

PCCA (HGNC:8653): (propionyl-CoA carboxylase subunit alpha) The protein encoded by this gene is the alpha subunit of the heterodimeric mitochondrial enzyme Propionyl-CoA carboxylase. PCCA encodes the biotin-binding region of this enzyme. Mutations in either PCCA or PCCB (encoding the beta subunit) lead to an enzyme deficiency resulting in propionic acidemia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

PCCA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16371182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCCA	NM_000282.4 linkuse as main transcript	c.17T>C	p.Val6Ala	missense_variant	1/24	ENST00000376285.6	NP_000273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCCA	ENST00000376285.6 linkuse as main transcript	c.17T>C	p.Val6Ala	missense_variant	1/24	1	NM_000282.4	ENSP00000365462	P1	P05165-1
PCCA	ENST00000376286.8 linkuse as main transcript	c.17T>C	p.Val6Ala	missense_variant	1/23	2		ENSP00000365463		P05165-2
PCCA	ENST00000376279.7 linkuse as main transcript	c.17T>C	p.Val6Ala	missense_variant	1/23	2		ENSP00000365456		P05165-3
PCCA	ENST00000647303.1 linkuse as main transcript	c.17T>C	p.Val6Ala	missense_variant, NMD_transcript_variant	1/21			ENSP00000495663

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1357508

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

667086

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2022

The c.17T>C (p.V6A) alteration is located in exon 1 (coding exon 1) of the PCCA gene. This alteration results from a T to C substitution at nucleotide position 17, causing the valine (V) at amino acid position 6 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Benign

5.1

DANN

Benign

0.69

DEOGEN2

Benign

0.36

.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0099

LIST_S2

Benign

0.54

T;T;T

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Uncertain

-0.0079

MutationAssessor

Benign

0.81

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.89

N;N;N

REVEL

Benign

0.27

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.20

MutPred

0.29

Gain of disorder (P = 0.0361);Gain of disorder (P = 0.0361);Gain of disorder (P = 0.0361);

MVP

0.77

MPC

0.17

ClinPred

0.038

GERP RS

-0.32

Varity_R

0.038

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over