20-2483484-A-C

Variant names:

• chr20-2483484-A-C
• NM_024325.6:c.1477T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024325.6(ZNF343):​c.1477T>G​(p.Tyr493Asp) 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 benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF343 NM_024325.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.804
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26702031).

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.1477T>G	p.Tyr493Asp	missense	Exon 6 of 6	NP_077301.4
	ZNF343	NM_001282497.2		c.1600T>G	p.Tyr534Asp	missense	Exon 7 of 7	NP_001269426.1	A0A087WZQ2
	ZNF343	NM_001321801.2		c.1600T>G	p.Tyr534Asp	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.1477T>G	p.Tyr493Asp	missense	Exon 6 of 6	ENSP00000278772.4	Q6P1L6-1
	ENSG00000256566	ENST00000461548.1	TSL:5	n.304+9215T>G		intron	N/A	ENSP00000456213.1	F5H5K5
	ZNF343	ENST00000612935.4	TSL:5	c.1600T>G	p.Tyr534Asp	missense	Exon 8 of 8	ENSP00000482819.1	A0A087WZQ2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	Pathogenic	0.77
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		0.80
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-8.4	D
REVEL	Benign	0.19
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.021	D
Polyphen		0.97	D
Vest4		0.33
MutPred		0.58		Gain of ubiquitination at K491 (P = 0.022)
MVP		0.24
MPC		0.52
ClinPred		0.85	D
GERP RS		-4.8
Varity_R		0.35
gMVP		0.16
Mutation Taster		=97/3	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: chr20-2464130;