Genetic Variant NM_003446.4:c.329T>C (chrX-47412402-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003446.4(ZNF157):c.329T>C(p.Val110Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,206,194 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

ZNF157
NM_003446.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.44

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051914603).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003446.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF157	NM_003446.4	MANE Select	c.329T>C	p.Val110Ala	missense	Exon 4 of 4	NP_003437.2	P51786

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF157	ENST00000377073.4	TSL:1 MANE Select	c.329T>C	p.Val110Ala	missense	Exon 4 of 4	ENSP00000366273.4	P51786

Frequencies

GnomAD3 genomes

AF:

0.00000887

AC:

AN:

112759

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.15e-7

AC:

AN:

1093435

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

359595

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26287

American (AMR)

AF:

0.00

AC:

AN:

35007

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19250

East Asian (EAS)

AF:

0.00

AC:

AN:

30096

South Asian (SAS)

AF:

0.00

AC:

AN:

53752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4109

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

838576

Other (OTH)

AF:

0.00

AC:

AN:

45880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000887

AC:

AN:

112759

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34921

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31099

American (AMR)

AF:

0.00

AC:

AN:

10579

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2663

East Asian (EAS)

AF:

0.00

AC:

AN:

3620

South Asian (SAS)

AF:

0.00

AC:

AN:

2771

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000187

AC:

AN:

53398

Other (OTH)

AF:

0.00

AC:

AN:

1525

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.96

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.11

M_CAP

Benign

0.0017

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.2

PhyloP100

-2.4

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.40

REVEL

Benign

0.033

Sift

Benign

0.34

Sift4G

Benign

0.46

Polyphen

0.0

Vest4

0.029

MutPred

0.36

Gain of disorder (P = 0.0304)

MVP

0.50

MPC

0.029

ClinPred

0.060

GERP RS

0.0087

Varity_R

0.036

gMVP

0.35

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over