chr19-21423268-T-A

Variant names:

• chr19-21423268-T-A
• rs140677584
• NM_001076678.3:c.609T>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001076678.3(ZNF493):​c.609T>A​(p.Ile203Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000899 in 1,613,796 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000060 (1 hom.)
• Consequence: ZNF493 NM_001076678.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.74
• Publications: 1 publications found

Genes affected

ZNF493 (HGNC:23708): (zinc finger protein 493) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269237 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-21423268-T-A is Benign according to our data. Variant chr19-21423268-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2649621.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.74 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF493	NM_001076678.3	c.609T>A	p.Ile203Ile	synonymous_variant	Exon 4 of 4	ENST00000392288.7	NP_001070146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF493	ENST00000392288.7	c.609T>A	p.Ile203Ile	synonymous_variant	Exon 4 of 4	1	NM_001076678.3	ENSP00000376110.2
ZNF493	ENST00000355504.4	c.225T>A	p.Ile75Ile	synonymous_variant	Exon 2 of 2	1		ENSP00000347691.4
ENSG00000269237	ENST00000600810.1	n.196+17412T>A		intron_variant	Intron 2 of 4	3		ENSP00000473166.1
ZNF493	ENST00000596302.5	c.*367T>A		downstream_gene_variant		1		ENSP00000469368.1

Frequencies

GnomAD3 genomes AF: 0.000374 AC: 57 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000955

GnomAD2 exomes AF: 0.0000961 AC: 24 AN: 249858 AF XY: 0.0000739

Gnomad AFR exome AF: 0.00133

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000595 AC: 87 AN: 1461466 Hom.: 1 Cov.: 32 AF XY: 0.0000495 AC XY: 36 AN XY: 727014

African (AFR) AF: 0.00185 AC: 62 AN: 33446

American (AMR) AF: 0.0000224 AC: 1 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5760

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111840

Other (OTH) AF: 0.000265 AC: 16 AN: 60372

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152330 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74494

African (AFR) AF: 0.00132 AC: 55 AN: 41576

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.000480

Asia WGS AF: 0.000289 AC: 1 AN: 3476

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZNF493: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.42
PhyloP100		-1.7

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: rs140677584; hg19: chr19-21606070;