rs12595786

Positions:

• chr15-84793439-T-C
• chr15-84793439-T-G

Variant summary

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

The NM_014630.3(ZNF592):​c.2399+2556T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,134 control chromosomes in the GnomAD database, including 21,302 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 0.52 (21302 hom., cov: 33)
• Consequence: ZNF592 NM_014630.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF592	NM_014630.3	c.2399+2556T>C		intron_variant		ENST00000560079.7	NP_055445.2
ZNF592	XM_005254996.4	c.2399+2556T>C		intron_variant			XP_005255053.1
ZNF592	XM_011522246.3	c.2399+2556T>C		intron_variant			XP_011520548.1
ZNF592	XM_011522247.3	c.2399+2556T>C		intron_variant			XP_011520549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF592	ENST00000560079.7	c.2399+2556T>C		intron_variant		1	NM_014630.3	ENSP00000452877	P1
ZNF592	ENST00000559607.1	c.2388+2567T>C		intron_variant, NMD_transcript_variant		1		ENSP00000453491
ZNF592	ENST00000299927.4	c.2399+2556T>C		intron_variant		2		ENSP00000299927	P1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79277 AN: 152014 Hom.: 21268 Cov.: 33

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.522 AC: 79366 AN: 152134 Hom.: 21302 Cov.: 33 AF XY: 0.525 AC XY: 39016 AN XY: 74378

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.490

Alfa AF: 0.456 Hom.: 9798

Bravo AF: 0.528

Asia WGS AF: 0.664 AC: 2304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.67

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: rs12595786; hg19: chr15-85336670;