Variant chr16-30555757-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001172679.2(ZNF764):c.661C>T(p.Arg221Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000825 in 1,455,274 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ZNF764
NM_001172679.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.72

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:

ZNF764 (HGNC:):

ZNF764 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF764	NM_001172679.2 linkuse as main transcript	c.661C>T	p.Arg221Trp	missense_variant	3/3	ENST00000395091.3	NP_001166150.1	Q96H86-2
ZNF764	NM_033410.4 linkuse as main transcript	c.664C>T	p.Arg222Trp	missense_variant	3/3		NP_219363.2	Q96H86-1A0A024QZB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF764	ENST00000395091.3 linkuse as main transcript	c.661C>T	p.Arg221Trp	missense_variant	3/3	2	NM_001172679.2	ENSP00000378526.2	Q96H86-2
ZNF764	ENST00000252797.6 linkuse as main transcript	c.664C>T	p.Arg222Trp	missense_variant	3/3	1		ENSP00000252797.2	Q96H86-1
ZNF764	ENST00000568333.1 linkuse as main transcript	n.830C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000331

AC:

AN:

241340

Hom.:

AF XY:

0.0000457

AC XY:

AN XY:

131276

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000169

Gnomad SAS exome

AF:

0.000100

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000338

GnomAD4 exome

AF:

0.00000825

AC:

AN:

1455274

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

723872

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000998

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2023

The c.664C>T (p.R222W) alteration is located in exon 3 (coding exon 3) of the ZNF764 gene. This alteration results from a C to T substitution at nucleotide position 664, causing the arginine (R) at amino acid position 222 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

T;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

0.92

N;N

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Benign

0.13

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.36

MutPred

0.45

Loss of disorder (P = 0.0109);.;

MVP

0.70

MPC

0.79

ClinPred

0.75

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.42

gMVP

0.43

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