Genetic Variant PCCA:p.Trp5Cys (chr13-100089135-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000282.4(PCCA):c.15G>T(p.Trp5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PCCA
NM_000282.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01

Publications

0 publications found

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:

PCCA-DT (HGNC:53266): (PCCA divergent transcript)

PCCA-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCCA	NM_000282.4 link	c.15G>T	p.Trp5Cys	missense_variant	Exon 1 of 24	ENST00000376285.6	NP_000273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCA	ENST00000376285.6 link	c.15G>T	p.Trp5Cys	missense_variant	Exon 1 of 24	1	NM_000282.4	ENSP00000365462.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

134074

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1359574

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668212

African (AFR)

AF:

0.00

AC:

AN:

28698

American (AMR)

AF:

0.00

AC:

AN:

33348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23798

East Asian (EAS)

AF:

0.00

AC:

AN:

32856

South Asian (SAS)

AF:

0.00

AC:

AN:

73564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1060914

Other (OTH)

AF:

0.00

AC:

AN:

56240

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Benign

(source)

DANN

Benign

0.61

DEOGEN2

Uncertain

0.44

.;.;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.76

T;T;T

M_CAP

Pathogenic

0.65

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Uncertain

0.35

MutationAssessor

Benign

0.90

L;L;L

PhyloP100

2.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.6

N;N;N

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.42

MutPred

0.51

Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);

MVP

0.91

MPC

0.23

ClinPred

0.48

GERP RS

2.9

PromoterAI

-0.0020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.66

Mutation Taster

=91/9

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over