Variant X-47412427-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003446.4(ZNF157):c.354T>A(p.Asp118Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,210,513 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 91 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 6 hem., cov: 24)

Exomes 𝑓: 0.00028 ( 0 hom. 85 hem. )

Consequence

ZNF157
NM_003446.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.413

Variant links:

Genes affected

ZNF157 (HGNC:12942): (zinc finger protein 157) This gene product is a likely zinc finger family transcription factor. It contains KRAB-A and KRAB-B domains that act as transcriptional repressors in related proteins, and multiple zinc finger DNA binding motifs and finger linking regions characteristic of the Kruppel family. This gene is part of a gene cluster on chromosome Xp11.23. [provided by RefSeq, Jul 2008]

ZNF157 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03285405).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF157	NM_003446.4 link	c.354T>A	p.Asp118Glu	missense_variant	4/4	ENST00000377073.4	NP_003437.2	P51786

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF157	ENST00000377073.4 link	c.354T>A	p.Asp118Glu	missense_variant	4/4	1	NM_003446.4	ENSP00000366273.4		P51786

Frequencies

GnomAD3 genomes

AF:

0.000168

AC:

AN:

112793

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

AN XY:

34933

show subpopulations

Gnomad AFR

AF:

0.0000643

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000162

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000299

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000126

AC:

AN:

182982

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

67474

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000730

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000626

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000276

AC:

303

AN:

1097720

Hom.:

Cov.:

AF XY:

0.000234

AC XY:

AN XY:

363118

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000740

Gnomad4 NFE exome

AF:

0.000347

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.000168

AC:

AN:

112793

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

AN XY:

34933

show subpopulations

Gnomad4 AFR

AF:

0.0000643

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000162

Gnomad4 NFE

AF:

0.000299

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000227

Hom.:

Bravo

AF:

0.000140

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.354T>A (p.D118E) alteration is located in exon 4 (coding exon 4) of the ZNF157 gene. This alteration results from a T to A substitution at nucleotide position 354, causing the aspartic acid (D) at amino acid position 118 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.99

CADD

Benign

2.2

DANN

Benign

0.34

DEOGEN2

Benign

0.0075

FATHMM_MKL

Benign

0.00043

LIST_S2

Benign

0.028

M_CAP

Benign

0.0020

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.085

PrimateAI

Benign

0.29

PROVEAN

Benign

0.14

REVEL

Benign

0.0080

Sift

Benign

0.75

Sift4G

Benign

0.86

Polyphen

0.0

Vest4

0.070

MutPred

0.26

Gain of solvent accessibility (P = 0.1376);

MVP

0.18

MPC

0.026

ClinPred

0.0073

GERP RS

0.26

Varity_R

0.050

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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