Variant 8-100709528-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_002568.4(PABPC1):c.1176T>G(p.Val392=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 131,260 control chromosomes in the GnomAD database, including 623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.067 ( 623 hom., cov: 33)

Exomes 𝑓: 0.11 ( 533 hom. )

Failed GnomAD Quality Control

Consequence

PABPC1
NM_002568.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.967

Variant links:

Genes affected

PABPC1 (HGNC:8554): (poly(A) binding protein cytoplasmic 1) This gene encodes a poly(A) binding protein. The protein shuttles between the nucleus and cytoplasm and binds to the 3' poly(A) tail of eukaryotic messenger RNAs via RNA-recognition motifs. The binding of this protein to poly(A) promotes ribosome recruitment and translation initiation; it is also required for poly(A) shortening which is the first step in mRNA decay. The gene is part of a small gene family including three protein-coding genes and several pseudogenes.[provided by RefSeq, Aug 2010]

PABPC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 8-100709528-A-C is Benign according to our data. Variant chr8-100709528-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3356114.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.967 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PABPC1	NM_002568.4 linkuse as main transcript	c.1176T>G	p.Val392=	synonymous_variant	8/15	ENST00000318607.10
PABPC1	XM_005250861.4 linkuse as main transcript	c.1176T>G	p.Val392=	synonymous_variant	8/15
PABPC1	XM_047421694.1 linkuse as main transcript	c.1176T>G	p.Val392=	synonymous_variant	8/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PABPC1	ENST00000318607.10 linkuse as main transcript	c.1176T>G	p.Val392=	synonymous_variant	8/15	1	NM_002568.4	P1	P11940-1

Frequencies

GnomAD3 genomes

AF:

0.0673

AC:

8829

AN:

131166

Hom.:

617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0379

Gnomad ASJ

AF:

0.00594

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.0569

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.105

AC:

90984

AN:

864356

Hom.:

533

Cov.:

AF XY:

0.113

AC XY:

49318

AN XY:

434880

show subpopulations

Gnomad4 AFR exome

AF:

0.331

Gnomad4 AMR exome

AF:

0.220

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.0679

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.0858

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.0674

AC:

8848

AN:

131260

Hom.:

623

Cov.:

AF XY:

0.0679

AC XY:

4308

AN XY:

63406

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.0379

Gnomad4 ASJ

AF:

0.00594

Gnomad4 EAS

AF:

0.0156

Gnomad4 SAS

AF:

0.0142

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.0109

Gnomad4 OTH

AF:

0.0580

Alfa

AF:

0.303

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PABPC1-related condition

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 16, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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