Variant chr19-57504781-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000282292.9(ZNF773):c.158C>G(p.Ser53Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,052 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000023 ( 1 hom. )

Consequence

ZNF773
ENST00000282292.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Variant links:

Genes affected

ZNF773 (HGNC:30487): (zinc finger protein 773) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF773 links:

ENSG00000268107 (HGNC:):

ENSG00000268107 links:

Genome browser will be placed here

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
ZNF773	NM_198542.3 linkuse as main transcript	c.158C>G	p.Ser53Cys	missense_variant	2/4	ENST00000282292.9	NP_940944.1	Q6PK81-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF773	ENST00000282292.9 linkuse as main transcript	c.158C>G	p.Ser53Cys	missense_variant	2/4	1	NM_198542.3	ENSP00000282292.3	Q6PK81-1
ENSG00000268107	ENST00000601674.6 linkuse as main transcript	n.*105C>G		non_coding_transcript_exon_variant	3/6	2		ENSP00000471625.1	M0R143
ENSG00000268107	ENST00000601674.6 linkuse as main transcript	n.*105C>G		3_prime_UTR_variant	3/6	2		ENSP00000471625.1	M0R143

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151302

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:

0.0000955

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000677

AC:

AN:

250958

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.0000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151302

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73828

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000955

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Oct 25, 2022

The c.158C>G (p.S53C) alteration is located in exon 2 (coding exon 2) of the ZNF773 gene. This alteration results from a C to G substitution at nucleotide position 158, causing the serine (S) at amino acid position 53 to be replaced by a cysteine (C). 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

0.20

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

.;.;.;T

Eigen

Benign

-0.042

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.70

T;T;.;T

M_CAP

Benign

0.0017

MetaRNN

Uncertain

0.70

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.3

.;.;.;M

MutationTaster

Benign

0.91

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-4.5

.;.;.;D

REVEL

Benign

0.073

Sift

Pathogenic

0.0

.;.;.;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

.;D;.;D

Vest4

0.60

MutPred

0.75

.;.;Loss of disorder (P = 0.0091);Loss of disorder (P = 0.0091);

MVP

0.47

MPC

0.31

ClinPred

0.54

GERP RS

1.4

Varity_R

0.45

gMVP

0.098

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