rs3748376

Variant names:

• chr15-84785121-C-T
• rs3748376
• NM_014630.3:c.2220+226C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0290
• Publications: 15 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 -20 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 VariationId is 1245527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ZNF592	NM_014630.3	c.2220+226C>T		intron_variant	Intron 4 of 10	ENST00000560079.7	NP_055445.2
ZNF592	XM_005254996.4	c.2220+226C>T		intron_variant	Intron 3 of 9		XP_005255053.1
ZNF592	XM_011522246.3	c.2220+226C>T		intron_variant	Intron 4 of 10		XP_011520548.1
ZNF592	XM_011522247.3	c.2220+226C>T		intron_variant	Intron 3 of 9		XP_011520549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF592	ENST00000560079.7	c.2220+226C>T		intron_variant	Intron 4 of 10	1	NM_014630.3	ENSP00000452877.2
ZNF592	ENST00000559607.1	n.2220+226C>T		intron_variant	Intron 2 of 8	1		ENSP00000453491.1
ZNF592	ENST00000299927.4	c.2220+226C>T		intron_variant	Intron 1 of 7	2		ENSP00000299927.3

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

African (AFR) AF: 0.0478 AC: 1986 AN: 41510

American (AMR) AF: 0.175 AC: 2670 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3472

East Asian (EAS) AF: 0.119 AC: 614 AN: 5164

South Asian (SAS) AF: 0.191 AC: 920 AN: 4818

European-Finnish (FIN) AF: 0.248 AC: 2617 AN: 10556

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18870 AN: 67984

Other (OTH) AF: 0.208 AC: 438 AN: 2106

Alfa AF: 0.254 Hom.: 2676

Bravo AF: 0.185

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.4
DANN	Benign	0.44
PhyloP100		-0.029
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: rs3748376; hg19: chr15-85328352;