20-2483283-G-A

Variant names:

• chr20-2483283-G-A
• rs146638299
• NM_024325.6:c.1678C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024325.6(ZNF343):​c.1678C>T​(p.Arg560Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,610,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R560Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000087 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: ZNF343 NM_024325.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.17
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049395174).

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.1678C>T	p.Arg560Trp	missense	Exon 6 of 6	NP_077301.4
	ZNF343	NM_001282497.2		c.1801C>T	p.Arg601Trp	missense	Exon 7 of 7	NP_001269426.1	A0A087WZQ2
	ZNF343	NM_001321801.2		c.1801C>T	p.Arg601Trp	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.1678C>T	p.Arg560Trp	missense	Exon 6 of 6	ENSP00000278772.4	Q6P1L6-1
	ENSG00000256566	ENST00000461548.1	TSL:5	n.304+9416C>T		intron	N/A	ENSP00000456213.1	F5H5K5
	ZNF343	ENST00000612935.4	TSL:5	c.1801C>T	p.Arg601Trp	missense	Exon 8 of 8	ENSP00000482819.1	A0A087WZQ2

Frequencies

GnomAD3 genomes AF: 0.0000867 AC: 13 AN: 150018 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000271

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: 0.0000296

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000399 AC: 10 AN: 250876 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000445 AC: 65 AN: 1460334 Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 32 AN XY: 726502

African (AFR) AF: 0.000269 AC: 9 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39526

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 86020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

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

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1111552

Other (OTH) AF: 0.0000166 AC: 1 AN: 60314

GnomAD4 genome AF: 0.0000867 AC: 13 AN: 150018 Hom.: 0 Cov.: 32 AF XY: 0.0000820 AC XY: 6 AN XY: 73136

African (AFR) AF: 0.000271 AC: 11 AN: 40640

American (AMR) AF: 0.00 AC: 0 AN: 15036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5024

South Asian (SAS) AF: 0.00 AC: 0 AN: 4730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67470

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.000189

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.0000545

EpiControl AF: 0.0000594

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	Uncertain	0.54
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.84
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.49	N
PhyloP100		-2.2
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.042
Sift	Benign	0.041	D
Sift4G	Benign	0.20	T
Polyphen		0.073	B
Vest4		0.068
MVP		0.35
MPC		0.072
ClinPred		0.033	T
GERP RS		0.28
Varity_R		0.029
gMVP		0.078
Mutation Taster		=96/4	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: rs146638299; hg19: chr20-2463929;