chr20-2483534-C-T

Variant names:

• chr20-2483534-C-T
• rs374101325
• NM_024325.6:c.1427G>A

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.1427G>A​(p.Arg476Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,591,172 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: 𝑓 0.000031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ZNF343 NM_024325.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.64
• 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=0.032479435).

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.1427G>A	p.Arg476Gln	missense	Exon 6 of 6	NP_077301.4
	ZNF343	NM_001282497.2		c.1550G>A	p.Arg517Gln	missense	Exon 7 of 7	NP_001269426.1	A0A087WZQ2
	ZNF343	NM_001321801.2		c.1550G>A	p.Arg517Gln	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.1427G>A	p.Arg476Gln	missense	Exon 6 of 6	ENSP00000278772.4	Q6P1L6-1
	ENSG00000256566	ENST00000461548.1	TSL:5	n.304+9165G>A		intron	N/A	ENSP00000456213.1	F5H5K5
	ZNF343	ENST00000612935.4	TSL:5	c.1550G>A	p.Arg517Gln	missense	Exon 8 of 8	ENSP00000482819.1	A0A087WZQ2

Frequencies

GnomAD3 genomes AF: 0.0000306 AC: 4 AN: 130588 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000654

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251416 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460584 Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11 AN XY: 726620

African (AFR) AF: 0.00 AC: 0 AN: 33384

American (AMR) AF: 0.0000224 AC: 1 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111254

Other (OTH) AF: 0.0000332 AC: 2 AN: 60262

GnomAD4 genome AF: 0.0000306 AC: 4 AN: 130588 Hom.: 0 Cov.: 32 AF XY: 0.0000158 AC XY: 1 AN XY: 63306

African (AFR) AF: 0.00 AC: 0 AN: 33668

American (AMR) AF: 0.00 AC: 0 AN: 13084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3240

East Asian (EAS) AF: 0.00 AC: 0 AN: 4338

South Asian (SAS) AF: 0.00 AC: 0 AN: 4140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 174

European-Non Finnish (NFE) AF: 0.0000654 AC: 4 AN: 61136

Other (OTH) AF: 0.00 AC: 0 AN: 1822

Alfa AF: 0.000122 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000412 AC: 5

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	0.27
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.6
DANN	Benign	0.74
DEOGEN2	Benign	0.00055	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.58	N
PhyloP100		-1.6
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.017
Sift	Benign	1.0	T
Sift4G	Benign	0.80	T
Polyphen		0.025	B
Vest4		0.020
MVP		0.15
MPC		0.077
ClinPred		0.014	T
GERP RS		-3.5
Varity_R		0.023
gMVP		0.033
Mutation Taster		=100/0	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

dbSNP: rs374101325; hg19: chr20-2464180;