Variant X-47410290-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003446.4(ZNF157):c.87C>A(p.Phe29Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,209,055 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 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: -0.779

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.876

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF157	NM_003446.4 linkuse as main transcript	c.87C>A	p.Phe29Leu	missense_variant	2/4	ENST00000377073.4	NP_003437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF157	ENST00000377073.4 linkuse as main transcript	c.87C>A	p.Phe29Leu	missense_variant	2/4	1	NM_003446.4	ENSP00000366273	P1

Frequencies

GnomAD3 genomes

AF:

0.00000901

AC:

AN:

110974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33168

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000971

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183378

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098081

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363441

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000901

AC:

AN:

110974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33168

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000971

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

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

Sep 29, 2023

The c.87C>A (p.F29L) alteration is located in exon 2 (coding exon 2) of the ZNF157 gene. This alteration results from a C to A substitution at nucleotide position 87, causing the phenylalanine (F) at amino acid position 29 to be replaced by a leucine (L). 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

Pathogenic

0.97

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.75

M_CAP

Benign

0.0038

MetaRNN

Pathogenic

0.88

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-5.4

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.013

Polyphen

1.0

Vest4

0.64

MutPred

0.81

Gain of disorder (P = 0.2269);

MVP

0.50

MPC

0.22

ClinPred

0.99

GERP RS

-4.4

Varity_R

0.65

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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