rs7249379

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001367172.2(ZNF763):c.625G>T(p.Val209Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,614,160 control chromosomes in the GnomAD database, including 314 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 34 hom., cov: 32)

Exomes 𝑓: 0.018 ( 280 hom. )

Consequence

ZNF763
NM_001367172.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

ZNF763 (HGNC:27614): (zinc finger protein 763) 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]

ZNF763 links:

ENSG00000267179 (HGNC:):

ENSG00000267179 links:

ZNF69 (HGNC:13138): (zinc finger protein 69) Enables identical protein binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF69 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044953227).

BP6

Variant 19-11978549-G-T is Benign according to our data. Variant chr19-11978549-G-T is described in ClinVar as [Benign]. Clinvar id is 773349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0188 (2866/152288) while in subpopulation AFR AF = 0.0259 (1075/41564). AF 95% confidence interval is 0.0246. There are 34 homozygotes in GnomAd4. There are 1363 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF763	NM_001367172.2 link	c.625G>T	p.Val209Phe	missense_variant	Exon 4 of 4	ENST00000358987.8	NP_001354101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF763	ENST00000358987.8 link	c.625G>T	p.Val209Phe	missense_variant	Exon 4 of 4	1	NM_001367172.2	ENSP00000402017.1		Q0D2J5-1
ENSG00000267179	ENST00000590798.1 link	c.685G>T	p.Val229Phe	missense_variant	Exon 4 of 4	2		ENSP00000467286.1		F5H0A9

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2857

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0259

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0201

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00906

Gnomad SAS

AF:

0.0248

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.0177

GnomAD2 exomes

AF:

0.0165

AC:

4155

AN:

251406

AF XY:

0.0169

show subpopulations

Gnomad AFR exome

AF:

0.0255

Gnomad AMR exome

AF:

0.0124

Gnomad ASJ exome

AF:

0.00685

Gnomad EAS exome

AF:

0.00810

Gnomad FIN exome

AF:

0.00587

Gnomad NFE exome

AF:

0.0181

Gnomad OTH exome

AF:

0.0171

GnomAD4 exome

AF:

0.0180

AC:

26323

AN:

1461872

Hom.:

280

Cov.:

AF XY:

0.0179

AC XY:

13052

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.0269

AC:

901

AN:

33480

American (AMR)

AF:

0.0129

AC:

578

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00872

AC:

228

AN:

26134

East Asian (EAS)

AF:

0.00471

AC:

187

AN:

39694

South Asian (SAS)

AF:

0.0239

AC:

2061

AN:

86256

European-Finnish (FIN)

AF:

0.00636

AC:

340

AN:

53418

Middle Eastern (MID)

AF:

0.00641

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0187

AC:

20817

AN:

1112002

Other (OTH)

AF:

0.0194

AC:

1174

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1693

3386

5078

6771

8464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0188

AC:

2866

AN:

152288

Hom.:

Cov.:

AF XY:

0.0183

AC XY:

1363

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0259

AC:

1075

AN:

41564

American (AMR)

AF:

0.0200

AC:

306

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.00888

AC:

AN:

5178

South Asian (SAS)

AF:

0.0242

AC:

117

AN:

4826

European-Finnish (FIN)

AF:

0.00386

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0175

AC:

1193

AN:

68016

Other (OTH)

AF:

0.0227

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

154

307

461

614

768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0166

Hom.:

Bravo

AF:

0.0198

ExAC

AF:

0.0167

AC:

2033

EpiCase

AF:

0.0185

EpiControl

AF:

0.0184

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 01, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.15

(source)

DANN

Benign

0.11

DEOGEN2

Benign

0.033

.;.;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.000020

LIST_S2

Benign

0.11

T;T;T

MetaRNN

Benign

0.0045

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-3.0

.;.;N

PhyloP100

1.0

PROVEAN

Benign

4.6

.;N;N

REVEL

Benign

0.095

Sift

Benign

1.0

.;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.057

MPC

0.0087

ClinPred

0.0027

GERP RS

1.3

Varity_R

0.050

gMVP

0.013

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

Loading publications...

rs7249379

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over