Variant X-91435582-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_080832.3(PABPC5):c.5G>A(p.Gly2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 1,199,731 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Consequence

PABPC5
NM_080832.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21875203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PABPC5	NM_080832.3 linkuse as main transcript	c.5G>A	p.Gly2Glu	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.5G>A	p.Gly2Glu	missense_variant	2/2	1	NM_080832.3	P1	Q96DU9-1
PABPC5	ENST00000373105.1 linkuse as main transcript	c.-31-457G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000900

AC:

AN:

111154

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

33368

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:

0.000284

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

GnomAD3 exomes

AF:

0.00000581

AC:

AN:

172011

Hom.:

AF XY:

0.0000173

AC XY:

AN XY:

57745

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000734

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.19e-7

AC:

AN:

1088518

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

355702

show subpopulations

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:

0.00000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000899

AC:

AN:

111213

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33437

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000285

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

AC:

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

Apr 25, 2023

The c.5G>A (p.G2E) alteration is located in exon 2 (coding exon 1) of the PABPC5 gene. This alteration results from a G to A substitution at nucleotide position 5, causing the glycine (G) at amino acid position 2 to be replaced by a glutamic acid (E). 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

0.097

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.34

REVEL

Benign

0.085

Sift

Uncertain

0.011

Sift4G

Uncertain

0.0060

Polyphen

0.96

Vest4

0.28

MutPred

0.27

Gain of solvent accessibility (P = 0.0456);

MVP

0.79

MPC

1.8

ClinPred

0.64

GERP RS

4.6

Varity_R

0.20

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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