15-84787514-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014630.3(ZNF592):c.2220+2619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,964 control chromosomes in the GnomAD database, including 25,722 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (25722 hom., cov: 31)
• Consequence: ZNF592 NM_014630.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF592	NM_014630.3	c.2220+2619C>T		intron_variant		ENST00000560079.7
ZNF592	XM_005254996.4	c.2220+2619C>T		intron_variant
ZNF592	XM_011522246.3	c.2220+2619C>T		intron_variant
ZNF592	XM_011522247.3	c.2220+2619C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF592	ENST00000560079.7	c.2220+2619C>T		intron_variant		1	NM_014630.3	P1
ZNF592	ENST00000559607.1	c.2220+2619C>T		intron_variant, NMD_transcript_variant		1
ZNF592	ENST00000299927.4	c.2220+2619C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85978 AN: 151846 Hom.: 25678 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.527

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.566 AC: 86078 AN: 151964 Hom.: 25722 Cov.: 31 AF XY: 0.567 AC XY: 42115 AN XY: 74246

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.527

Alfa AF: 0.474 Hom.: 23224

Bravo AF: 0.579

Asia WGS AF: 0.673 AC: 2338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.9
Dann	Benign	0.38

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: rs10438428; hg19: chr15-85330745;