dbSNP rs373685372: PCCB:p.Ala3Glu (chr3-136250383-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000532.5(PCCB):c.8C>A(p.Ala3Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,373,198 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

PCCB
NM_000532.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.437

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35559922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCCB	NM_000532.5 link	c.8C>A	p.Ala3Glu	missense_variant	Exon 1 of 15	ENST00000251654.9	NP_000523.2	P05166-1
PCCB	NM_001178014.2 link	c.8C>A	p.Ala3Glu	missense_variant	Exon 1 of 16		NP_001171485.1	P05166-2
PCCB	XM_011512873.2 link	c.8C>A	p.Ala3Glu	missense_variant	Exon 1 of 11		XP_011511175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCB	ENST00000251654.9 link	c.8C>A	p.Ala3Glu	missense_variant	Exon 1 of 15	1	NM_000532.5	ENSP00000251654.4		P05166-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000218

AC:

AN:

1373198

Hom.:

Cov.:

AF XY:

0.00000445

AC XY:

AN XY:

673910

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000581

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:

9.40e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.34

T;.;.;T;T;T;.;.;.;.;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.83

T;D;T;D;T;T;T;T;T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.36

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.39

MutationAssessor

Benign

0.0

N;.;.;.;.;.;.;.;N;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.49

N;N;N;N;N;N;N;N;N;N;N

REVEL

Uncertain

0.54

Sift

Uncertain

0.021

D;D;D;D;D;D;D;D;D;D;D

Sift4G

Benign

0.13

T;D;T;D;T;D;D;D;D;D;D

Polyphen

0.53

P;.;.;.;.;.;.;P;.;.;.

Vest4

0.49

MutPred

0.41

Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);

MVP

0.95

MPC

0.12

ClinPred

0.75

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.20

gMVP

0.85

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over