Variant 19-57504734-G-T 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.111G>T(p.Arg37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZNF773
ENST00000282292.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0460

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:

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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
ZNF773	NM_198542.3 linkuse as main transcript	c.111G>T	p.Arg37Ser	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.111G>T	p.Arg37Ser	missense_variant	2/4	1	NM_198542.3	ENSP00000282292.3	Q6PK81-1
ENSG00000268107	ENST00000601674.6 linkuse as main transcript	n.*58G>T		non_coding_transcript_exon_variant	3/6	2		ENSP00000471625.1	M0R143
ENSG00000268107	ENST00000601674.6 linkuse as main transcript	n.*58G>T		3_prime_UTR_variant	3/6	2		ENSP00000471625.1	M0R143

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251466

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135908

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:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

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

Aug 22, 2023

The c.111G>T (p.R37S) alteration is located in exon 2 (coding exon 2) of the ZNF773 gene. This alteration results from a G to T substitution at nucleotide position 111, causing the arginine (R) at amino acid position 37 to be replaced by a serine (S). 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

Pathogenic

0.97

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.14

.;.;.;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.69

T;T;.;T

M_CAP

Benign

0.0016

MetaRNN

Uncertain

0.49

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

4.9

.;.;.;H

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-5.0

.;.;.;D

REVEL

Benign

0.086

Sift

Uncertain

0.0010

.;.;.;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

0.95, 0.34

.;P;.;B

Vest4

0.47

MutPred

0.71

.;.;Loss of helix (P = 0.028);Loss of helix (P = 0.028);

MVP

0.50

MPC

0.19

ClinPred

0.92

GERP RS

-1.1

Varity_R

0.50

gMVP

0.35

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