Variant 19-2916131-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_173480.3(ZNF57):c.184G>A(p.Gly62Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ZNF57
NM_173480.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.341

Variant links:

Genes affected

ZNF57 (HGNC:13125): (zinc finger protein 57) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF57 links:

ENSG00000253392 (HGNC:):

ENSG00000253392 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039709).

BP6

Variant 19-2916131-G-A is Benign according to our data. Variant chr19-2916131-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3258710.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF57	NM_173480.3 linkuse as main transcript	c.184G>A	p.Gly62Arg	missense_variant	3/4	ENST00000306908.10	NP_775751.1	Q68EA5A5HJR3
ZNF57	NM_001319083.2 linkuse as main transcript	c.88G>A	p.Gly30Arg	missense_variant	3/4		NP_001306012.1	Q68EA5G3V131A5HJR3B4DXX0
ZNF57	XM_011527682.3 linkuse as main transcript	c.88G>A	p.Gly30Arg	missense_variant	3/4		XP_011525984.1	G3V131

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF57	ENST00000306908.10 linkuse as main transcript	c.184G>A	p.Gly62Arg	missense_variant	3/4	1	NM_173480.3	ENSP00000303696.5		Q68EA5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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:

0.0000517

AC:

AN:

251218

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135780

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:

0.000114

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461654

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151968

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.5

DANN

Benign

0.93

DEOGEN2

Benign

0.0031

.;T;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.42

T;T;T;T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.040

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.20

.;N;.;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.7

.;N;D;N;.

REVEL

Benign

0.012

Sift

Benign

0.50

.;T;T;T;.

Sift4G

Benign

0.41

T;T;T;T;T

Polyphen

0.0010

.;B;.;.;.

Vest4

0.057

MutPred

0.33

Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);.;.;.;

MVP

0.17

MPC

0.032

ClinPred

0.025

GERP RS

0.23

Varity_R

0.038

gMVP

0.069

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