rs75652600

Variant names:

• chr15-84768060-A-T
• rs75652600
• NM_014630.3:c.-150+3245A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014630.3(ZNF592):​c.-150+3245A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 99,646 control chromosomes in the GnomAD database, including 2 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 0.0051 (2 hom., cov: 23)
• Consequence: ZNF592 NM_014630.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF592	NM_014630.3	c.-150+3245A>T		intron_variant	Intron 2 of 10	ENST00000560079.7	NP_055445.2
ZNF592	XM_005254996.4	c.-20+3245A>T		intron_variant	Intron 2 of 9		XP_005255053.1
ZNF592	XM_011522246.3	c.-150+3245A>T		intron_variant	Intron 2 of 10		XP_011520548.1
ZNF592	XM_011522247.3	c.-20+3245A>T		intron_variant	Intron 2 of 9		XP_011520549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF592	ENST00000560079.7	c.-150+3245A>T		intron_variant	Intron 2 of 10	1	NM_014630.3	ENSP00000452877.2

Frequencies

GnomAD3 genomes AF: 0.00514 AC: 511 AN: 99506 Hom.: 2 Cov.: 23

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00213

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000253

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000694

Gnomad MID AF: 0.00694

Gnomad NFE AF: 0.000635

Gnomad OTH AF: 0.00564

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

GnomAD4 genome AF: 0.00513 AC: 511 AN: 99646 Hom.: 2 Cov.: 23 AF XY: 0.00475 AC XY: 232 AN XY: 48812

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0123 AC: 453 AN: 36708

American (AMR) AF: 0.00213 AC: 22 AN: 10344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1800

East Asian (EAS) AF: 0.000253 AC: 1 AN: 3952

South Asian (SAS) AF: 0.00 AC: 0 AN: 3186

European-Finnish (FIN) AF: 0.000694 AC: 4 AN: 5764

Middle Eastern (MID) AF: 0.00725 AC: 1 AN: 138

European-Non Finnish (NFE) AF: 0.000636 AC: 23 AN: 36186

Other (OTH) AF: 0.00553 AC: 7 AN: 1266

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.198 Hom.: 115

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.81
DANN	Benign	0.15
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism

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: rs75652600; hg19: chr15-85311291;