Variant 20-2483214-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024325.6(ZNF343):c.1747G>A(p.Gly583Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000884 in 1,459,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000088 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF343
NM_024325.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

Variant links:

Genes affected

ZNF343 (HGNC:16017): (zinc finger protein 343) Enables sequence-specific double-stranded 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]

ZNF343 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052803665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF343	NM_024325.6 linkuse as main transcript	c.1747G>A	p.Gly583Arg	missense_variant	6/6	ENST00000278772.9	NP_077301.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF343	ENST00000278772.9 linkuse as main transcript	c.1747G>A	p.Gly583Arg	missense_variant	6/6	2	NM_024325.6	ENSP00000278772	P1	Q6P1L6-1
ZNF343	ENST00000612935.4 linkuse as main transcript	c.1870G>A	p.Gly624Arg	missense_variant	8/8	5		ENSP00000482819
ZNF343	ENST00000617391.4 linkuse as main transcript	c.1477G>A	p.Gly493Arg	missense_variant	4/4	4		ENSP00000483851		Q6P1L6-2
ZNF343	ENST00000465019.1 linkuse as main transcript	n.1775G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151178

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00117

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000164

AC:

AN:

250620

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135422

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000872

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000884

AC:

129

AN:

1459928

Hom.:

Cov.:

AF XY:

0.0000744

AC XY:

AN XY:

726258

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000226

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.000556

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000549

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000172

AC:

AN:

151296

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

73912

show subpopulations

Gnomad4 AFR

AF:

0.000315

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00117

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000119

Hom.:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000164

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

Jun 24, 2022

The c.1747G>A (p.G583R) alteration is located in exon 6 (coding exon 4) of the ZNF343 gene. This alteration results from a G to A substitution at nucleotide position 1747, causing the glycine (G) at amino acid position 583 to be replaced by an arginine (R). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.057

T;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.053

T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.4

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-4.8

D;.;.

REVEL

Benign

0.25

Sift

Benign

0.055

T;.;.

Sift4G

Benign

0.095

T;T;T

Polyphen

0.99

D;.;.

Vest4

0.18

MutPred

0.64

Gain of MoRF binding (P = 0.0235);.;.;

MVP

0.47

MPC

0.44

ClinPred

0.36

GERP RS

0.44

Varity_R

0.15

gMVP

0.032

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