Variant chr1-42850981-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_001242739.2(ZNF691):c.116G>A(p.Ser39Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,540,956 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ZNF691
NM_001242739.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.514

Variant links:

Genes affected

ZNF691 (HGNC:28028): (zinc finger protein 691) 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]

ZNF691 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity ZN691_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008751005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF691	NM_001242739.2 linkuse as main transcript	c.116G>A	p.Ser39Asn	missense_variant	4/4	ENST00000651192.1	NP_001229668.1	Q5VV52-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF691	ENST00000651192.1 linkuse as main transcript	c.116G>A	p.Ser39Asn	missense_variant	4/4		NM_001242739.2	ENSP00000498913.1		Q5VV52-2

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000165

AC:

AN:

187938

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

99122

show subpopulations

Gnomad AFR exome

AF:

0.00187

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:

0.0000111

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000238

AC:

AN:

1388626

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

684240

show subpopulations

Gnomad4 AFR exome

AF:

0.000875

Gnomad4 AMR exome

AF:

0.0000311

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:

9.26e-7

Gnomad4 OTH exome

AF:

0.0000700

GnomAD4 genome

AF:

0.000328

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000150

Hom.:

Bravo

AF:

0.000366

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000133

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Dec 03, 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

0.088

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.7

DANN

Benign

0.94

DEOGEN2

Benign

0.018

T;.;.;.;T;T;T;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.56

T;.;.;T;.;T;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.0088

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;.;.;.;.;.;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.070

.;N;N;N;N;N;N;.

REVEL

Benign

0.14

Sift

Benign

0.085

.;T;T;T;T;T;T;.

Sift4G

Benign

0.43

T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;.;.;.

Vest4

0.035

MVP

0.014

ClinPred

0.0036

GERP RS

-2.4

Varity_R

0.032

gMVP

0.11

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