Variant 5-43175092-G-C 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_001330707.2(ZNF131):c.1831G>C(p.Ala611Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000432 in 1,614,130 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 2 hom. )

Consequence

ZNF131
NM_001330707.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.284

Variant links:

Genes affected

ZNF131 (HGNC:12915): (zinc finger protein 131) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription repressor activity, RNA polymerase II-specific; and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Located in intermediate filament cytoskeleton and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF131 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=0.0034110248).

BP6

Variant 5-43175092-G-C is Benign according to our data. Variant chr5-43175092-G-C is described in ClinVar as [Benign]. Clinvar id is 787816.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF131	NM_001330707.2 link	c.1831G>C	p.Ala611Pro	missense_variant	7/7	ENST00000682664.1	NP_001317636.1	P52739-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF131	ENST00000682664.1 link	c.1831G>C	p.Ala611Pro	missense_variant	7/7		NM_001330707.2	ENSP00000507111.1		P52739-1

Frequencies

GnomAD3 genomes

AF:

0.00228

AC:

347

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00809

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000554

AC:

138

AN:

248932

Hom.:

AF XY:

0.000429

AC XY:

AN XY:

135122

show subpopulations

Gnomad AFR exome

AF:

0.00769

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000240

AC:

351

AN:

1461830

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

145

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00890

Gnomad4 AMR exome

AF:

0.000425

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:

0.00000270

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.00228

AC:

347

AN:

152300

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00806

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.00262

ESP6500AA

AF:

0.00655

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000588

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.1

DANN

Benign

0.73

DEOGEN2

Benign

0.013

T;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.57

T;.;.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0034

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.81

L;.;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.52

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.070

T;T;T;T

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

0.0

B;B;B;B

Vest4

0.12

MVP

0.28

MPC

0.69

ClinPred

0.00043

GERP RS

-2.9

Varity_R

0.043

gMVP

0.12

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