Variant chr4-372823-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003441.4(ZNF141):c.386G>A(p.Gly129Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,613,382 control chromosomes in the GnomAD database, including 4 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 4 hom. )

Consequence

ZNF141
NM_003441.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0400

Variant links:

Genes affected

ZNF141 (HGNC:12926): (zinc finger protein 141) The protein encoded by this gene is a zinc finger protein that may be a tumor suppressor. Defects in this gene have been associated with autosomal recessive postaxial polydactyly type A. [provided by RefSeq, Jan 2017]

ZNF141 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008481622).

BP6

Variant 4-372823-G-A is Benign according to our data. Variant chr4-372823-G-A is described in ClinVar as [Benign]. Clinvar id is 718907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF141	NM_003441.4 linkuse as main transcript	c.386G>A	p.Gly129Asp	missense_variant	4/4	ENST00000240499.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF141	ENST00000240499.8 linkuse as main transcript	c.386G>A	p.Gly129Asp	missense_variant	4/4	1	NM_003441.4	P1
ZNF141	ENST00000512994.5 linkuse as main transcript	c.386G>A	p.Gly129Asp	missense_variant	4/5	1
ZNF141	ENST00000505939.5 linkuse as main transcript	c.227-10272G>A		intron_variant		5
ZNF141	ENST00000366506.4 linkuse as main transcript	n.333G>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

231

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00203

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00191

AC:

478

AN:

250732

Hom.:

AF XY:

0.00178

AC XY:

242

AN XY:

135578

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000295

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00213

Gnomad OTH exome

AF:

0.00541

GnomAD4 exome

AF:

0.00157

AC:

2296

AN:

1461084

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

1149

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00202

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00153

Gnomad4 OTH exome

AF:

0.00268

GnomAD4 genome

AF:

0.00152

AC:

231

AN:

152298

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00203

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00258

Hom.:

Bravo

AF:

0.00186

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00180

AC:

218

EpiCase

AF:

0.00338

EpiControl

AF:

0.00255

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

ZNF141-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 08, 2019

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

CADD

Benign

3.3

DANN

Uncertain

0.99

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.00076

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0085

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-5.8

D;D

REVEL

Benign

0.066

Sift

Benign

0.11

T;T

Sift4G

Benign

0.063

T;T

Polyphen

1.0

D;D

Vest4

0.16

MVP

0.33

MPC

0.46

ClinPred

0.091

GERP RS

1.2

Varity_R

0.14

gMVP

0.0051

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