NM_024325.6:c.1655G>C

Variant names:

• chr20-2483306-C-G
• NM_024325.6:c.1655G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 17/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.25
• Publications: 0 publications found

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]

ENSG00000256566 (HGNC:):

ACMG classification

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=0.039191544).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF343	NM_024325.6	MANE Select	c.1655G>C	p.Ser552Thr	missense	Exon 6 of 6	NP_077301.4
	ZNF343	NM_001282497.2		c.1778G>C	p.Ser593Thr	missense	Exon 7 of 7	NP_001269426.1	A0A087WZQ2
	ZNF343	NM_001321801.2		c.1778G>C	p.Ser593Thr	missense	Exon 7 of 7	NP_001308730.1	A0A087WZQ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF343	ENST00000278772.9	TSL:2 MANE Select	c.1655G>C	p.Ser552Thr	missense	Exon 6 of 6	ENSP00000278772.4	Q6P1L6-1
	ENSG00000256566	ENST00000461548.1	TSL:5	n.304+9393G>C		intron	N/A	ENSP00000456213.1	F5H5K5
	ZNF343	ENST00000612935.4	TSL:5	c.1778G>C	p.Ser593Thr	missense	Exon 8 of 8	ENSP00000482819.1	A0A087WZQ2

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

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.00 AC: 0 AN: 86030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111618

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.35	N
PhyloP100		-4.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.052
Sift	Benign	0.42	T
Sift4G	Benign	0.44	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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

hg19: chr20-2463952;