Variant X-91435948-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_080832.3(PABPC5):c.371A>G(p.Tyr124Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000895 in 111,786 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Consequence

PABPC5
NM_080832.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.04

Variant links:

Genes affected

PABPC5 (HGNC:13629): (poly(A) binding protein cytoplasmic 5) This gene encodes a protein that binds to the polyA tail found at the 3' end of most eukaryotic mRNAs. It is thought to play a role in the regulation of mRNA metabolic processes in the cytoplasm. This gene is located in a gene-poor region within the X-specific 13d-sY43 subinterval of the chromosome Xq21.3/Yp11.2 homology block. It is located close to translocation breakpoints associated with premature ovarian failure, and is therefore a potential candidate gene for this disorder. [provided by RefSeq, May 2010]

PABPC5 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=0.41635302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PABPC5	NM_080832.3 linkuse as main transcript	c.371A>G	p.Tyr124Cys	missense_variant	2/2	ENST00000312600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PABPC5	ENST00000312600.4 linkuse as main transcript	c.371A>G	p.Tyr124Cys	missense_variant	2/2	1	NM_080832.3	P1	Q96DU9-1
PABPC5	ENST00000373105.1 linkuse as main transcript	c.-31-91A>G		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111786

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33974

show subpopulations

Gnomad AFR

AF:

0.0000325

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111786

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33974

show subpopulations

Gnomad4 AFR

AF:

0.0000325

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.371A>G (p.Y124C) alteration is located in exon 2 (coding exon 1) of the PABPC5 gene. This alteration results from a A to G substitution at nucleotide position 371, causing the tyrosine (Y) at amino acid position 124 to be replaced by a cysteine (C). 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

0.17

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.023

MetaRNN

Benign

0.42

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.59

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.40

MutPred

0.50

Gain of catalytic residue at L125 (P = 0.026);

MVP

0.91

MPC

1.8

ClinPred

0.91

GERP RS

4.4

Varity_R

0.71

gMVP

0.89

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