rs12595786

Variant names:

• chr15-84793439-T-C
• rs12595786
• NM_014630.3:c.2399+2556T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF592	NM_014630.3	c.2399+2556T>C		intron_variant	Intron 5 of 10	ENST00000560079.7	NP_055445.2
ZNF592	XM_005254996.4	c.2399+2556T>C		intron_variant	Intron 4 of 9		XP_005255053.1
ZNF592	XM_011522246.3	c.2399+2556T>C		intron_variant	Intron 5 of 10		XP_011520548.1
ZNF592	XM_011522247.3	c.2399+2556T>C		intron_variant	Intron 4 of 9		XP_011520549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF592	ENST00000560079.7	c.2399+2556T>C		intron_variant	Intron 5 of 10	1	NM_014630.3	ENSP00000452877.2
ZNF592	ENST00000559607.1	n.2388+2567T>C		intron_variant	Intron 3 of 8	1		ENSP00000453491.1
ZNF592	ENST00000299927.4	c.2399+2556T>C		intron_variant	Intron 2 of 7	2		ENSP00000299927.3

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

African (AFR) AF: 0.629 AC: 26102 AN: 41486

American (AMR) AF: 0.517 AC: 7903 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3470

East Asian (EAS) AF: 0.789 AC: 4091 AN: 5186

South Asian (SAS) AF: 0.539 AC: 2599 AN: 4822

European-Finnish (FIN) AF: 0.456 AC: 4824 AN: 10574

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30878 AN: 68000

Other (OTH) AF: 0.490 AC: 1035 AN: 2112

Alfa AF: 0.460 Hom.: 12069

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
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs12595786; hg19: chr15-85336670;