20-2483217-A-G

Position:

• chr20-2483217-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024325.6(ZNF343):​c.1744T>C​(p.Cys582Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF343 NM_024325.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF343	NM_024325.6	c.1744T>C	p.Cys582Arg	missense_variant	6/6	ENST00000278772.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF343	ENST00000278772.9	c.1744T>C	p.Cys582Arg	missense_variant	6/6	2	NM_024325.6	P1
ZNF343	ENST00000612935.4	c.1867T>C	p.Cys623Arg	missense_variant	8/8	5
ZNF343	ENST00000617391.4	c.1474T>C	p.Cys492Arg	missense_variant	4/4	4
ZNF343	ENST00000465019.1	n.1772T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.1744T>C (p.C582R) alteration is located in exon 6 (coding exon 4) of the ZNF343 gene. This alteration results from a T to C substitution at nucleotide position 1744, causing the cysteine (C) at amino acid position 582 to be replaced by an arginine (R). 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	0.89
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.27	T;.;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	-0.060
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.53	T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Pathogenic	4.0	H;.;.
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-10	D;.;.
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D;.;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.48
MutPred		0.76		Gain of MoRF binding (P = 0.0087);.;.;
MVP		0.92
MPC		0.53
ClinPred		0.98	D
GERP RS		1.5
Varity_R		0.82
gMVP		0.15

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: chr20-2463863;