rs3748376

chr15-84785121-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014630.3(ZNF592):c.2220+226C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,102 control chromosomes in the GnomAD database, including 3,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3642 hom., cov: 32)
• Consequence: ZNF592 NM_014630.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0290

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-84785121-C-T is Benign according to our data. Variant chr15-84785121-C-T is described in ClinVar as [Benign]. Clinvar id is 1245527.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF592	NM_014630.3	c.2220+226C>T		intron_variant		ENST00000560079.7
ZNF592	XM_005254996.4	c.2220+226C>T		intron_variant
ZNF592	XM_011522246.3	c.2220+226C>T		intron_variant
ZNF592	XM_011522247.3	c.2220+226C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF592	ENST00000560079.7	c.2220+226C>T		intron_variant		1	NM_014630.3	P1
ZNF592	ENST00000559607.1	c.2220+226C>T		intron_variant, NMD_transcript_variant		1
ZNF592	ENST00000299927.4	c.2220+226C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29635 AN: 151984 Hom.: 3643 Cov.: 32

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.195 AC: 29623 AN: 152102 Hom.: 3642 Cov.: 32 AF XY: 0.192 AC XY: 14258 AN XY: 74336

Gnomad4 AFR AF: 0.0478

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.208

Alfa AF: 0.253 Hom.: 2416

Bravo AF: 0.185

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.4
Dann	Benign	0.44

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: rs3748376; hg19: chr15-85328352;