Variant 20-2483370-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF343	NM_024325.6 link	c.1591T>A	p.Cys531Ser	missense_variant	6/6	ENST00000278772.9	NP_077301.4	Q6P1L6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF343	ENST00000278772.9 link	c.1591T>A	p.Cys531Ser	missense_variant	6/6	2	NM_024325.6	ENSP00000278772.4		Q6P1L6-1
ENSG00000256566	ENST00000461548.1 link	n.304+9329T>A		intron_variant		5		ENSP00000456213.1		F5H5K5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148694

Hom.:

Cov.:

FAILED QC

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

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

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

Jul 26, 2024

The c.1591T>A (p.C531S) alteration is located in exon 6 (coding exon 4) of the ZNF343 gene. This alteration results from a T to A substitution at nucleotide position 1591, causing the cysteine (C) at amino acid position 531 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

Benign

0.28

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.0

DANN

Benign

0.80

DEOGEN2

Benign

0.00033

T;.;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.014

T;T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.025

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.3

N;.;.

PrimateAI

Benign

0.37

PROVEAN

Benign

0.49

N;.;.

REVEL

Benign

0.015

Sift

Benign

0.81

T;.;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

B;.;.

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

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over