19-11487473-G-C

Position:

• chr19-11487473-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The ENST00000293771.10(ZNF653):​c.990C>G​(p.Leu330Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,613,490 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (10 hom.)
• Consequence: ZNF653 ENST00000293771.10 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.931

Genes affected

ZNF653 (HGNC:25196): (zinc finger protein 653) Enables AF-2 domain binding activity and transcription corepressor activity. Involved in extracellular negative regulation of signal transduction and negative regulation of nucleic acid-templated transcription. Predicted to be located in extracellular region. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267477 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 19-11487473-G-C is Benign according to our data. Variant chr19-11487473-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2649331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.931 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF653	NM_138783.4	c.990C>G	p.Leu330Leu	synonymous_variant	4/9	ENST00000293771.10	NP_620138.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF653	ENST00000293771.10	c.990C>G	p.Leu330Leu	synonymous_variant	4/9	1	NM_138783.4	ENSP00000293771.3
ENSG00000267477	ENST00000585656.1	n.469+8477C>G		intron_variant		5		ENSP00000466387.1
ZNF653	ENST00000590548.5	n.1025C>G		non_coding_transcript_exon_variant	4/8	2

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 246 AN: 152230 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000719

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00285

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00166 AC: 417 AN: 250490 Hom.: 2 AF XY: 0.00168 AC XY: 228 AN XY: 135494

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00356

Gnomad NFE exome AF: 0.00254

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00158 AC: 2306 AN: 1461142 Hom.: 10 Cov.: 33 AF XY: 0.00164 AC XY: 1193 AN XY: 726902

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.00130

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00265

Gnomad4 NFE exome AF: 0.00181

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.00161 AC: 246 AN: 152348 Hom.: 1 Cov.: 33 AF XY: 0.00157 AC XY: 117 AN XY: 74506

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000718

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00292

Gnomad4 NFE AF: 0.00285

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00216 Hom.: 0

Bravo AF: 0.00130

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00213

EpiControl AF: 0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

ZNF653: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.51
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs145806085; hg19: chr19-11598288;