Genetic Variant ZNF343:p.Cys531Ser (chr20-2483370-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024325.6(ZNF343):c.1591T>A(p.Cys531Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

ZNF343
NM_024325.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.857

Publications

0 publications found

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:

ENSG00000256566 (HGNC:):

ENSG00000256566 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025292397).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024325.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF343	NM_024325.6	MANE Select	c.1591T>A	p.Cys531Ser	missense	Exon 6 of 6	NP_077301.4
ZNF343	NM_001282497.2		c.1714T>A	p.Cys572Ser	missense	Exon 7 of 7	NP_001269426.1	A0A087WZQ2
ZNF343	NM_001321801.2		c.1714T>A	p.Cys572Ser	missense	Exon 7 of 7	NP_001308730.1	A0A087WZQ2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF343	ENST00000278772.9	TSL:2 MANE Select	c.1591T>A	p.Cys531Ser	missense	Exon 6 of 6	ENSP00000278772.4	Q6P1L6-1
ENSG00000256566	ENST00000461548.1	TSL:5	n.304+9329T>A		intron	N/A	ENSP00000456213.1	F5H5K5
ZNF343	ENST00000612935.4	TSL:5	c.1714T>A	p.Cys572Ser	missense	Exon 8 of 8	ENSP00000482819.1	A0A087WZQ2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148694

Hom.:

Cov.:

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

148806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72566

African (AFR)

AF:

0.00

AC:

AN:

40062

American (AMR)

AF:

0.00

AC:

AN:

14912

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

5052

South Asian (SAS)

AF:

0.00

AC:

AN:

4686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67296

Other (OTH)

AF:

0.00

AC:

AN:

2054

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.0

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.00033

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.014

M_CAP

Benign

0.0018

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.3

PhyloP100

0.86

PrimateAI

Benign

0.37

PROVEAN

Benign

0.49

REVEL

Benign

0.015

Sift

Benign

0.81

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.098

MutPred

0.38

Gain of catalytic residue at C531 (P = 0.0117)

MVP

0.076

MPC

0.081

ClinPred

0.055

GERP RS

-5.5

Varity_R

0.041

gMVP

0.014

Mutation Taster

=95/5

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over