chr1-246987457-C-T

Position:

chr1-246987457-C-T

Variant summary

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

The NM_020394.5(ZNF695):c.1058G>A(p.Arg353Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000472 in 1,610,030 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 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

ZNF695
NM_020394.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.81

Variant links:

Genes affected

ZNF695 (HGNC:30954): (zinc finger protein 695) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF695 links:

ZNF670-ZNF695 (HGNC:49200): (ZNF670-ZNF695 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring zinc finger protein 670 (ZNF670) and zinc finger protein 695 (ZNF695) genes on chromosome 1. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ZNF670-ZNF695 links:

ZNF695 (HGNC:):

ZNF695 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=0.014898241).

BP6

Variant 1-246987457-C-T is Benign according to our data. Variant chr1-246987457-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3197771.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF695	NM_020394.5 linkuse as main transcript	c.1058G>A	p.Arg353Gln	missense_variant	4/4	ENST00000339986.8	NP_065127.5
ZNF695	NM_001204221.2 linkuse as main transcript	c.390+668G>A		intron_variant			NP_001191150.2	Q8IW36-1
ZNF695	NR_037892.2 linkuse as main transcript	n.543+664G>A		intron_variant
ZNF670-ZNF695	NR_037894.2 linkuse as main transcript	n.573+664G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF695	ENST00000339986.8 linkuse as main transcript	c.1058G>A	p.Arg353Gln	missense_variant	4/4	1	NM_020394.5	ENSP00000341236.7		Q8IW36-4
ZNF670-ZNF695	ENST00000465049.6 linkuse as main transcript	n.358+664G>A		intron_variant		5		ENSP00000428213.1		F2Z2N8

Frequencies

GnomAD3 genomes

AF:

0.0000463

AC:

AN:

151074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000487

AC:

AN:

246180

Hom.:

AF XY:

0.0000674

AC XY:

AN XY:

133612

show subpopulations

Gnomad AFR exome

AF:

0.0000650

Gnomad AMR exome

AF:

0.000148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000660

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000359

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000473

AC:

AN:

1458840

Hom.:

Cov.:

AF XY:

0.0000634

AC XY:

AN XY:

725668

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000904

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000463

AC:

AN:

151190

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73854

show subpopulations

Gnomad4 AFR

AF:

0.0000486

Gnomad4 AMR

AF:

0.0000659

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000495

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

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

Sep 14, 2022

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

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.0011

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0

LIST_S2

Benign

0.093

M_CAP

Benign

0.0015

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.36

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.57

REVEL

Benign

0.029

Sift

Benign

0.14

Sift4G

Benign

0.096

Polyphen

0.0

Vest4

0.084

MVP

0.17

MPC

0.042

ClinPred

0.018

GERP RS

-0.73

Varity_R

0.031

gMVP

0.0053

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