20-2483350-A-G

Variant names:

• chr20-2483350-A-G
• rs763443890
• NM_024325.6:c.1611T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_024325.6(ZNF343):​c.1611T>C​(p.Ile537Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF343 NM_024325.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.59
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-2483350-A-G is Benign according to our data. Variant chr20-2483350-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3026083.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1611T>C	p.Ile537Ile	synonymous	Exon 6 of 6	NP_077301.4
	ZNF343	NM_001282497.2		c.1734T>C	p.Ile578Ile	synonymous	Exon 7 of 7	NP_001269426.1	A0A087WZQ2
	ZNF343	NM_001321801.2		c.1734T>C	p.Ile578Ile	synonymous	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.1611T>C	p.Ile537Ile	synonymous	Exon 6 of 6	ENSP00000278772.4	Q6P1L6-1
	ENSG00000256566	ENST00000461548.1	TSL:5	n.304+9349T>C		intron	N/A	ENSP00000456213.1	F5H5K5
	ZNF343	ENST00000612935.4	TSL:5	c.1734T>C	p.Ile578Ile	synonymous	Exon 8 of 8	ENSP00000482819.1	A0A087WZQ2

Frequencies

GnomAD3 genomes AF: 0.0000138 AC: 2 AN: 144616 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000520

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251376 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000616

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460466 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 726578

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44330

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 86070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

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

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111492

Other (OTH) AF: 0.0000166 AC: 1 AN: 60308

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000138 AC: 2 AN: 144742 Hom.: 0 Cov.: 32 AF XY: 0.0000284 AC XY: 2 AN XY: 70508

African (AFR) AF: 0.0000518 AC: 2 AN: 38606

American (AMR) AF: 0.00 AC: 0 AN: 14558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3386

East Asian (EAS) AF: 0.00 AC: 0 AN: 4804

South Asian (SAS) AF: 0.00 AC: 0 AN: 4524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66070

Other (OTH) AF: 0.00 AC: 0 AN: 1996

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.74
PhyloP100		-3.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs763443890; hg19: chr20-2463996;