Genetic Variant NM_001076678.3:c.617G>A (chr19-21423276-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001076678.3(ZNF493):c.617G>A(p.Arg206Lys) 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 1,461,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R206T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF493
NM_001076678.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.698

Publications

0 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:

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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=0.07124779).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF493	NM_001076678.3 link	c.617G>A	p.Arg206Lys	missense_variant	Exon 4 of 4	ENST00000392288.7	NP_001070146.1	Q6ZR52-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF493	ENST00000392288.7 link	c.617G>A	p.Arg206Lys	missense_variant	Exon 4 of 4	1	NM_001076678.3	ENSP00000376110.2	Q6ZR52-2
ZNF493	ENST00000355504.4 link	c.233G>A	p.Arg78Lys	missense_variant	Exon 2 of 2	1		ENSP00000347691.4	Q6ZR52-1
ENSG00000269237	ENST00000600810.1 link	n.196+17420G>A		intron_variant	Intron 2 of 4	3		ENSP00000473166.1	M0R3E3
ZNF493	ENST00000596302.5 link	c.*375G>A		downstream_gene_variant		1		ENSP00000469368.1	M0QXT4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461392

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726984

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111758

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.8

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.032

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.18

T;T

M_CAP

Benign

0.00076

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.14

.;N

PhyloP100

0.70

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.023

Sift

Benign

0.46

T;T

Sift4G

Benign

0.072

T;D

Polyphen

0.57

P;B

Vest4

0.043

MutPred

0.45

.;Gain of methylation at R78 (P = 0.0211);

MVP

0.18

MPC

0.021

ClinPred

0.030

GERP RS

-0.40

Varity_R

0.067

gMVP

0.0099

Mutation Taster

=100/0

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

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NM_001076678.3:c.617G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over