Genetic Variant ZNF764:p.Gly320Arg (chr16-30555460-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001172679.2(ZNF764):c.958G>A(p.Gly320Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000194 in 1,546,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF764
NM_001172679.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08

Publications

0 publications found

Variant links:

Genes affected

ZNF764 (HGNC:28200): (zinc finger protein 764) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA 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]

ZNF764 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.773

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172679.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF764	NM_001172679.2	MANE Select	c.958G>A	p.Gly320Arg	missense	Exon 3 of 3	NP_001166150.1	Q96H86-2
	ZNF764	NM_033410.4		c.961G>A	p.Gly321Arg	missense	Exon 3 of 3	NP_219363.2	Q96H86-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF764	ENST00000395091.3	TSL:2 MANE Select	c.958G>A	p.Gly320Arg	missense	Exon 3 of 3	ENSP00000378526.2	Q96H86-2
ZNF764	ENST00000252797.6	TSL:1	c.961G>A	p.Gly321Arg	missense	Exon 3 of 3	ENSP00000252797.2	Q96H86-1
ZNF764	ENST00000952475.1		c.844G>A	p.Gly282Arg	missense	Exon 2 of 2	ENSP00000622534.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1394416

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689840

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31728

American (AMR)

AF:

0.00

AC:

AN:

37194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22654

East Asian (EAS)

AF:

0.00

AC:

AN:

38852

South Asian (SAS)

AF:

0.0000129

AC:

AN:

77686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47884

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5476

European-Non Finnish (NFE)

AF:

9.30e-7

AC:

AN:

1075298

Other (OTH)

AF:

0.00

AC:

AN:

57644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.031

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.6

PhyloP100

6.1

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-7.3

REVEL

Benign

0.18

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.69

MutPred

0.62

Gain of MoRF binding (P = 0.0353)

MVP

0.76

MPC

0.85

ClinPred

1.0

GERP RS

4.9

Varity_R

0.83

gMVP

0.33

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over