20-44912666-G-A

Position:

chr20-44912666-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001372179.1(PABPC1L):c.200G>A(p.Arg67Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,610,376 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 2 hom. )

Consequence

PABPC1L
NM_001372179.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 8.03

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01576662).

BP6

Variant 20-44912666-G-A is Benign according to our data. Variant chr20-44912666-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2398557.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PABPC1L	NM_001372179.1 linkuse as main transcript	c.200G>A	p.Arg67Gln	missense_variant	2/15	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.200G>A	p.Arg67Gln	missense_variant	2/15	5	NM_001372179.1	ENSP00000217073.3	A0A6Q8JFT6
PABPC1L	ENST00000537323.5 linkuse as main transcript	n.200G>A		non_coding_transcript_exon_variant	2/14	1		ENSP00000445661.1	Q4VXU2-2
PABPC1L	ENST00000255136.8 linkuse as main transcript	c.200G>A	p.Arg67Gln	missense_variant	2/15	5		ENSP00000255136.3	Q4VXU2-1
PABPC1L	ENST00000217074.9 linkuse as main transcript	n.179G>A		non_coding_transcript_exon_variant	2/14	5		ENSP00000217074.5	A0A6Q8JFV4

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

177

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00175

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00128

AC:

317

AN:

248208

Hom.:

AF XY:

0.00128

AC XY:

173

AN XY:

134864

show subpopulations

Gnomad AFR exome

AF:

0.000519

Gnomad AMR exome

AF:

0.000871

Gnomad ASJ exome

AF:

0.00540

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000883

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00165

Gnomad OTH exome

AF:

0.00166

GnomAD4 exome

AF:

0.00181

AC:

2634

AN:

1458176

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

1283

AN XY:

725180

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.000852

Gnomad4 ASJ exome

AF:

0.00542

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000918

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.00204

Gnomad4 OTH exome

AF:

0.00158

GnomAD4 genome

AF:

0.00116

AC:

177

AN:

152200

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.00175

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00215

Hom.:

Bravo

AF:

0.00119

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000638

AC:

ESP6500EA

AF:

0.00223

AC:

ExAC

AF:

0.00126

AC:

152

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.200G>A (p.R67Q) alteration is located in exon 2 (coding exon 2) of the PABPC1L gene. This alteration results from a G to A substitution at nucleotide position 200, causing the arginine (R) at amino acid position 67 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

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

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.070

.;T;.;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

.;D;D;.

M_CAP

Benign

0.010

MetaRNN

Benign

0.016

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;L;L

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.012

D;D;D;D

Sift4G

Benign

0.070

T;D;T;D

Polyphen

0.97

.;D;.;D

Vest4

0.40

MVP

0.62

MPC

2.1

ClinPred

0.042

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.44

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