20-2483446-C-G

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

1
3
15

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]

Genome browser will be placed here

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
ZNF343NM_024325.6 linkc.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
ZNF343ENST00000278772.9 linkc.1515G>C p.Lys505Asn missense_variant Exon 6 of 6 2 NM_024325.6 ENSP00000278772.4 Q6P1L6-1
ENSG00000256566ENST00000461548.1 linkn.304+9253G>C intron_variant Intron 5 of 6 5 ENSP00000456213.1 F5H5K5

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
144388
Hom.:
0
Cov.:
32
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:
2
AN:
1460658
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
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:
1
AN:
144486
Hom.:
0
Cov.:
32
AF XY:
0.0000142
AC XY:
1
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.:
0
ExAC
AF:
0.0000165
AC:
2

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
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
14
DANN
Uncertain
1.0
DEOGEN2
Benign
0.036
T;.;.
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.090
N
LIST_S2
Benign
0.18
T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.93
L;.;.
PrimateAI
Benign
0.37
T
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
D
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.

Other links and lift over

dbSNP: rs754106908; hg19: chr20-2464092; API