15-84782858-C-T

Variant summary

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

The NM_014630.3(ZNF592):c.183C>T(p.Pro61=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000973 in 1,614,084 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00090 (5 hom.)
• Consequence: ZNF592 NM_014630.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42

Genes affected

ZNF592 (HGNC:28986): (zinc finger protein 592) This gene is thought to play a role in a complex developmental pathway and the regulation of genes involved in cerebellar development. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 15-84782858-C-T is Benign according to our data. Variant chr15-84782858-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645649.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.42 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF592	NM_014630.3	c.183C>T	p.Pro61=	synonymous_variant	4/11	ENST00000560079.7
ZNF592	XM_005254996.4	c.183C>T	p.Pro61=	synonymous_variant	3/10
ZNF592	XM_011522246.3	c.183C>T	p.Pro61=	synonymous_variant	4/11
ZNF592	XM_011522247.3	c.183C>T	p.Pro61=	synonymous_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF592	ENST00000560079.7	c.183C>T	p.Pro61=	synonymous_variant	4/11	1	NM_014630.3	P1
ZNF592	ENST00000559607.1	c.183C>T	p.Pro61=	synonymous_variant, NMD_transcript_variant	2/9	1
ZNF592	ENST00000299927.4	c.183C>T	p.Pro61=	synonymous_variant	1/8	2		P1

Frequencies

GnomAD3 genomes AF: 0.00168 AC: 256 AN: 152074 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

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: 0.00103

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000942 AC: 237 AN: 251480 Hom.: 2 AF XY: 0.000824 AC XY: 112 AN XY: 135914

Gnomad AFR exome AF: 0.00344

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000835

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.000900 AC: 1315 AN: 1461892 Hom.: 5 Cov.: 32 AF XY: 0.000844 AC XY: 614 AN XY: 727246

Gnomad4 AFR exome AF: 0.00326

Gnomad4 AMR exome AF: 0.00221

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.000913

Gnomad4 OTH exome AF: 0.00113

GnomAD4 genome AF: 0.00168 AC: 256 AN: 152192 Hom.: 1 Cov.: 32 AF XY: 0.00167 AC XY: 124 AN XY: 74406

Gnomad4 AFR AF: 0.00349

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00103

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00151 Hom.: 1

Bravo AF: 0.00200

EpiCase AF: 0.00115

EpiControl AF: 0.00107

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

Jul 01, 2022

ZNF592: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	5.7
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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

Publications

LitVar

Other links and lift over

dbSNP: rs144989451; hg19: chr15-85326089; COSMIC: COSV100246183;