Variant chr20-44918956-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001372179.1(PABPC1L):c.554C>T(p.Ala185Val) variant causes a missense change. The variant allele was found at a frequency of 0.00571 in 1,612,166 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 42 hom. )

Consequence

PABPC1L
NM_001372179.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.62

Variant links:

Genes affected

PABPC1L (HGNC:15797): (poly(A) binding protein cytoplasmic 1 like) This gene belongs to the polyadenylate-binding protein type-1 family of proteins. Members of this family bind to the polyA tails of mRNAs to regulate mRNA stability and translation. The mouse ortholog of this gene is required for female fertility. In human, expression of a functional protein is regulated by alternative splicing. The protein-coding splice variant for this gene is abundantly expressed in human oocytes, while a noncoding splice variant subject to nonsense-mediated decay is the predominant splice variant expressed in somatic tissues. [provided by RefSeq, Aug 2019]

PABPC1L links:

PABPC1L (HGNC:):

PABPC1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008015841).

BP6

Variant 20-44918956-C-T is Benign according to our data. Variant chr20-44918956-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652347.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 42 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PABPC1L	NM_001372179.1 linkuse as main transcript	c.554C>T	p.Ala185Val	missense_variant	4/15	ENST00000217073.7	NP_001359108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PABPC1L	ENST00000217073.7 linkuse as main transcript	c.554C>T	p.Ala185Val	missense_variant	4/15	5	NM_001372179.1	ENSP00000217073.3	A0A6Q8JFT6
PABPC1L	ENST00000537323.5 linkuse as main transcript	n.554C>T		non_coding_transcript_exon_variant	4/14	1		ENSP00000445661.1	Q4VXU2-2
PABPC1L	ENST00000255136.8 linkuse as main transcript	c.554C>T	p.Ala185Val	missense_variant	4/15	5		ENSP00000255136.3	Q4VXU2-1
PABPC1L	ENST00000217074.9 linkuse as main transcript	n.417C>T		non_coding_transcript_exon_variant	3/14	5		ENSP00000217074.5	A0A6Q8JFV4

Frequencies

GnomAD3 genomes

AF:

0.00412

AC:

626

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00661

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00625

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00414

AC:

1024

AN:

247132

Hom.:

AF XY:

0.00418

AC XY:

561

AN XY:

134210

show subpopulations

Gnomad AFR exome

AF:

0.000714

Gnomad AMR exome

AF:

0.00163

Gnomad ASJ exome

AF:

0.00385

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.00228

Gnomad FIN exome

AF:

0.00724

Gnomad NFE exome

AF:

0.00600

Gnomad OTH exome

AF:

0.00350

GnomAD4 exome

AF:

0.00588

AC:

8582

AN:

1459948

Hom.:

Cov.:

AF XY:

0.00573

AC XY:

4159

AN XY:

726140

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00200

Gnomad4 ASJ exome

AF:

0.00497

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00194

Gnomad4 FIN exome

AF:

0.00688

Gnomad4 NFE exome

AF:

0.00674

Gnomad4 OTH exome

AF:

0.00509

GnomAD4 genome

AF:

0.00411

AC:

625

AN:

152218

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

290

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00661

Gnomad4 NFE

AF:

0.00625

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00488

Hom.:

Bravo

AF:

0.00390

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00223

AC:

ESP6500EA

AF:

0.00600

AC:

ExAC

AF:

0.00395

AC:

476

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

PABPC1L: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

.;T;.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.80

.;T;T;.

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.0080

T;T;T;T

MetaSVM

Uncertain

0.18

MutationAssessor

Benign

1.4

L;L;L;L

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.1

N;N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.11

T;T;T;T

Sift4G

Benign

0.20

T;T;T;T

Polyphen

0.29

.;B;.;B

Vest4

0.087

MVP

0.64

MPC

0.26

ClinPred

0.018

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.046

gMVP

0.38

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