rs181874152

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001076678.3(ZNF493):c.86G>A(p.Cys29Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF493
NM_001076678.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.799

Publications

1 publications found

Variant links:

Genes affected

ZNF493 (HGNC:23708): (zinc finger protein 493) Predicted to enable DNA-binding transcription activator 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]

ZNF493 links:

ENSG00000269237 (HGNC:):

ENSG00000269237 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12155539).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF493	NM_001076678.3 link	c.86G>A	p.Cys29Tyr	missense_variant	Exon 2 of 4	ENST00000392288.7	NP_001070146.1	Q6ZR52-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF493	ENST00000392288.7 link	c.86G>A	p.Cys29Tyr	missense_variant	Exon 2 of 4	1	NM_001076678.3	ENSP00000376110.2		Q6ZR52-2
ENSG00000269237	ENST00000600810.1 link	n.26G>A		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000473166.1		M0R3E3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251422

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727202

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.0000447

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111964

Other (OTH)

AF:

0.00

AC:

AN:

60388

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.029673), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

Mar 31, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.86G>A (p.C29Y) alteration is located in exon 2 (coding exon 2) of the ZNF493 gene. This alteration results from a G to A substitution at nucleotide position 86, causing the cysteine (C) at amino acid position 29 to be replaced by a tyrosine (Y). 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

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.51

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.014

T;T;T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.97

PhyloP100

-0.80

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-7.6

.;D;.;D

REVEL

Benign

0.024

Sift

Benign

0.12

.;T;.;D

Sift4G

Benign

0.065

T;T;D;T

Polyphen

0.38

.;B;.;.

Vest4

0.22

MutPred

0.50

Loss of catalytic residue at L30 (P = 0.0588);Loss of catalytic residue at L30 (P = 0.0588);Loss of catalytic residue at L30 (P = 0.0588);Loss of catalytic residue at L30 (P = 0.0588);

MVP

0.14

MPC

0.082

ClinPred

0.13

GERP RS

-2.3

gMVP

0.078

Mutation Taster

=99/1

polymorphism

(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

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

rs181874152

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over