Genetic Variant ZNF343:p.Lys505Asn (chr20-2483446-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024325.6(ZNF343):c.1515G>C(p.Lys505Asn) 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 1,460,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 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: -1.68

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17697182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF343	NM_024325.6 link	c.1515G>C	p.Lys505Asn	missense_variant	Exon 6 of 6	ENST00000278772.9	NP_077301.4	Q6P1L6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF343	ENST00000278772.9 link	c.1515G>C	p.Lys505Asn	missense_variant	Exon 6 of 6	2	NM_024325.6	ENSP00000278772.4		Q6P1L6-1
ENSG00000256566	ENST00000461548.1 link	n.304+9253G>C		intron_variant	Intron 5 of 6	5		ENSP00000456213.1		F5H5K5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

144388

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000260

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

AF:

0.00000137

AC:

AN:

1460658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726662

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000692

AC:

AN:

144486

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70372

show subpopulations

Gnomad4 AFR

AF:

0.0000259

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

Alfa

AF:

0.000249

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1515G>C (p.K505N) alteration is located in exon 6 (coding exon 4) of the ZNF343 gene. This alteration results from a G to C substitution at nucleotide position 1515, causing the lysine (K) at amino acid position 505 to be replaced by an asparagine (N). 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

Pathogenic

0.77

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

T;.;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.18

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.93

L;.;.

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.4

D;.;.

REVEL

Benign

0.032

Sift

Uncertain

0.0010

D;.;.

Sift4G

Benign

0.077

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.040

MutPred

0.40

Loss of methylation at K505 (P = 0.0186);.;.;

MVP

0.65

MPC

0.16

ClinPred

0.76

GERP RS

0.36

Varity_R

0.46

gMVP

0.017

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