Variant chr19-51944424-G-T 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_001031721.4(ZNF613):c.541G>T(p.Gly181Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,607,268 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

ZNF613
NM_001031721.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.29

Variant links:

Genes affected

ZNF613 (HGNC:25827): (zinc finger protein 613) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF613 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=0.013721138).

BP6

Variant 19-51944424-G-T is Benign according to our data. Variant chr19-51944424-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2411814.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF613	NM_001031721.4 linkuse as main transcript	c.541G>T	p.Gly181Cys	missense_variant	6/6	ENST00000293471.11
ZNF613	NM_024840.4 linkuse as main transcript	c.433G>T	p.Gly145Cys	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF613	ENST00000293471.11 linkuse as main transcript	c.541G>T	p.Gly181Cys	missense_variant	6/6	1	NM_001031721.4	P1	Q6PF04-1
ZNF613	ENST00000391794.8 linkuse as main transcript	c.433G>T	p.Gly145Cys	missense_variant	6/6	2			Q6PF04-2

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000266

AC:

AN:

248306

Hom.:

AF XY:

0.000291

AC XY:

AN XY:

134126

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.0000586

Gnomad ASJ exome

AF:

0.00121

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000100

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.000365

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000219

AC:

319

AN:

1455092

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

156

AN XY:

722412

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.000807

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.000338

Gnomad4 NFE exome

AF:

0.000225

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000243

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000363

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000272

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

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

Oct 27, 2021

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

0.078

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.21

DANN

Benign

0.079

DEOGEN2

Benign

0.0023

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.076

T;T

M_CAP

Benign

0.00087

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.4

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.45

N;N

REVEL

Benign

0.018

Sift

Benign

0.48

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.076

MVP

0.19

MPC

0.089

ClinPred

0.29

GERP RS

-0.78

Varity_R

0.076

gMVP

0.035

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