rs8182086

Variant names:

• chr15-84798628-G-A
• rs8182086
• NM_014630.3:c.2777G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-84798628-G-A
• chr15-84798628-G-C

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.2777G>A​(p.Ser926Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,613,784 control chromosomes in the GnomAD database, including 55,769 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6480 hom., cov: 32)
  • Exomes 𝑓: 0.25 (49289 hom.)
• Consequence: ZNF592 NM_014630.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.961
• Publications: 46 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 (MetaRNN=0.0030214787).
• BP6: Variant 15-84798628-G-A is Benign according to our data. Variant chr15-84798628-G-A is described in ClinVar as Benign. ClinVar VariationId is 130840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014630.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF592	NM_014630.3	MANE Select	c.2777G>A	p.Ser926Asn	missense	Exon 8 of 11	NP_055445.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF592	ENST00000560079.7	TSL:1 MANE Select	c.2777G>A	p.Ser926Asn	missense	Exon 8 of 11	ENSP00000452877.2
	ZNF592	ENST00000559607.1	TSL:1	n.*189G>A		non_coding_transcript_exon	Exon 6 of 9	ENSP00000453491.1
	ZNF592	ENST00000559607.1	TSL:1	n.*189G>A		3_prime_UTR	Exon 6 of 9	ENSP00000453491.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42707 AN: 151980 Hom.: 6471 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.270

GnomAD2 exomes AF: 0.298 AC: 74756 AN: 251016 AF XY: 0.294

Gnomad AFR exome AF: 0.347

Gnomad AMR exome AF: 0.427

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.478

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.264

GnomAD4 exome AF: 0.251 AC: 367335 AN: 1461686 Hom.: 49289 Cov.: 46 AF XY: 0.254 AC XY: 184380 AN XY: 727144

African (AFR) AF: 0.348 AC: 11653 AN: 33480

American (AMR) AF: 0.414 AC: 18494 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5702 AN: 26136

East Asian (EAS) AF: 0.432 AC: 17136 AN: 39700

South Asian (SAS) AF: 0.395 AC: 34035 AN: 86256

European-Finnish (FIN) AF: 0.234 AC: 12457 AN: 53240

Middle Eastern (MID) AF: 0.174 AC: 1001 AN: 5768

European-Non Finnish (NFE) AF: 0.226 AC: 251056 AN: 1111990

Other (OTH) AF: 0.262 AC: 15801 AN: 60394

GnomAD4 genome AF: 0.281 AC: 42747 AN: 152098 Hom.: 6480 Cov.: 32 AF XY: 0.287 AC XY: 21355 AN XY: 74342

African (AFR) AF: 0.340 AC: 14109 AN: 41476

American (AMR) AF: 0.338 AC: 5173 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 777 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2369 AN: 5156

South Asian (SAS) AF: 0.411 AC: 1985 AN: 4824

European-Finnish (FIN) AF: 0.227 AC: 2403 AN: 10578

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15133 AN: 67982

Other (OTH) AF: 0.267 AC: 565 AN: 2114

Alfa AF: 0.242 Hom.: 15267

Bravo AF: 0.290

TwinsUK AF: 0.227 AC: 842

ALSPAC AF: 0.245 AC: 945

ESP6500AA AF: 0.328 AC: 1446

ESP6500EA AF: 0.219 AC: 1887

ExAC AF: 0.292 AC: 35470

Asia WGS AF: 0.425 AC: 1476 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Galloway-Mowat syndrome 1 Benign:1

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.0028
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.96
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.18
Sift	Benign	0.34	T
Sift4G	Benign	0.51	T
Polyphen		0.21	B
Vest4		0.13
MPC		0.90
ClinPred		0.014	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.34
Mutation Taster		=98/2	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: rs8182086; hg19: chr15-85341859; COSMIC: COSV55436471;