rs12193967

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142800.2(EYS):c.359C>T(p.Thr120Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,613,900 control chromosomes in the GnomAD database, including 37,656 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2880 hom., cov: 33)

Exomes 𝑓: 0.21 ( 34776 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.0200

Variant links:

Genes affected

EYS (HGNC:21555): (eyes shut homolog) The product of this gene contains multiple epidermal growth factor (EGF)-like and LamG domains. The protein is expressed in the photoreceptor layer of the retina, and the gene is mutated in autosomal recessive retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

EYS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052424073).

BP6

Variant 6-65495052-G-A is Benign according to our data. Variant chr6-65495052-G-A is described in ClinVar as [Benign]. Clinvar id is 137261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-65495052-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.359C>T	p.Thr120Met	missense_variant	Exon 4 of 43	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.359C>T	p.Thr120Met	missense_variant	Exon 4 of 44		NP_001278938.1	Q5T1H1-3
EYS	NM_001142801.2 link	c.359C>T	p.Thr120Met	missense_variant	Exon 4 of 12		NP_001136273.1	Q5T1H1-4
EYS	NM_198283.2 link	c.359C>T	p.Thr120Met	missense_variant	Exon 3 of 10		NP_938024.1	Q5T1H1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6 link	c.359C>T	p.Thr120Met	missense_variant	Exon 4 of 43	5	NM_001142800.2	ENSP00000424243.1		Q5T1H1-1

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26535

AN:

152026

Hom.:

2880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0401

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.223

GnomAD3 exomes

AF:

0.209

AC:

52423

AN:

251270

Hom.:

5991

AF XY:

0.207

AC XY:

28151

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0370

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.247

Gnomad EAS exome

AF:

0.247

Gnomad SAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.229

GnomAD4 exome

AF:

0.214

AC:

312650

AN:

1461754

Hom.:

34776

Cov.:

AF XY:

0.212

AC XY:

154514

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0364

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.254

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.219

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.174

AC:

26538

AN:

152146

Hom.:

2880

Cov.:

AF XY:

0.177

AC XY:

13132

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0400

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.271

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.220

Alfa

AF:

0.208

Hom.:

8561

Bravo

AF:

0.173

TwinsUK

AF:

0.219

AC:

811

ALSPAC

AF:

0.221

AC:

852

ESP6500AA

AF:

0.0449

AC:

198

ESP6500EA

AF:

0.220

AC:

1891

ExAC

AF:

0.203

AC:

24587

Asia WGS

AF:

0.186

AC:

649

AN:

3478

EpiCase

AF:

0.219

EpiControl

AF:

0.218

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jul 14, 2011

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 12, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Retinitis pigmentosa 25

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa

Benign:2

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

4.2

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

.;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.56

T;T;T;T

MetaRNN

Benign

0.0052

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.55

N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.92

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.19

T;T;T;T

Sift4G

Uncertain

0.039

D;D;T;T

Polyphen

0.063

B;.;.;B

Vest4

0.055

MPC

0.043

ClinPred

0.013

GERP RS

-1.7

Varity_R

0.015

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over