NM_024325.6:c.1655G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024325.6(ZNF343):​c.1655G>C​(p.Ser552Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF343
NM_024325.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.25
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]

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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=0.039191544).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF343NM_024325.6 linkc.1655G>C p.Ser552Thr 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.1655G>C p.Ser552Thr missense_variant Exon 6 of 6 2 NM_024325.6 ENSP00000278772.4 Q6P1L6-1
ENSG00000256566ENST00000461548.1 linkn.304+9393G>C intron_variant Intron 5 of 6 5 ENSP00000456213.1 F5H5K5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460464
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726556
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1655G>C (p.S552T) 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 1655, causing the serine (S) at amino acid position 552 to be replaced by a threonine (T). 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
0.10
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
0.20
DANN
Benign
0.76
DEOGEN2
Benign
0.0044
T;.;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.022
T;T;T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.039
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.35
N;.;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.99
N;.;.
REVEL
Benign
0.052
Sift
Benign
0.42
T;.;.
Sift4G
Benign
0.44
T;T;T
Polyphen
0.026
B;.;.
Vest4
0.10
MutPred
0.17
Loss of disorder (P = 0.0676);.;.;
MVP
0.13
MPC
0.067
ClinPred
0.077
T
GERP RS
-2.9
Varity_R
0.024
gMVP
0.018

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.

Other links and lift over

hg19: chr20-2463952; API