Variant 8-100712378-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP6

The NM_002568.4(PABPC1):c.956C>T(p.Thr319Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PABPC1
NM_002568.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 9.94

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.784

BP6

Variant 8-100712378-G-A is Benign according to our data. Variant chr8-100712378-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2681460.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PABPC1	NM_002568.4 linkuse as main transcript	c.956C>T	p.Thr319Ile	missense_variant	7/15	ENST00000318607.10
PABPC1	XM_005250861.4 linkuse as main transcript	c.956C>T	p.Thr319Ile	missense_variant	7/15
PABPC1	XM_047421694.1 linkuse as main transcript	c.956C>T	p.Thr319Ile	missense_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PABPC1	ENST00000318607.10 linkuse as main transcript	c.956C>T	p.Thr319Ile	missense_variant	7/15	1	NM_002568.4	P1	P11940-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000174

AC:

AN:

1152718

Hom.:

Cov.:

AF XY:

0.00000175

AC XY:

AN XY:

572684

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:

0.00000231

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma

Benign:1

Likely benign, no assertion criteria provided

research

Department of Clinical Pathology, School of Medicine, Fujita Health University

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T;T;T

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.34

T;T;T;T

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.78

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-4.7

D;D;D;.

REVEL

Uncertain

0.47

Sift

Uncertain

0.0040

D;D;D;.

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

0.97

D;.;P;.

Vest4

0.77

MVP

0.88

MPC

2.3

ClinPred

0.98

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.74

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