NM_001142800.2:c.359C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T120R) has been classified 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

Publications

28 publications found

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 Gene-Disease associations (from GenCC):

EYS-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa
Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
retinitis pigmentosa 25
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

EYS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 137261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142800.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EYS	NM_001142800.2	MANE Select	c.359C>T	p.Thr120Met	missense	Exon 4 of 43	NP_001136272.1
EYS	NM_001292009.2		c.359C>T	p.Thr120Met	missense	Exon 4 of 44	NP_001278938.1
EYS	NM_001142801.2		c.359C>T	p.Thr120Met	missense	Exon 4 of 12	NP_001136273.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EYS	ENST00000503581.6	TSL:5 MANE Select	c.359C>T	p.Thr120Met	missense	Exon 4 of 43	ENSP00000424243.1
EYS	ENST00000370621.7	TSL:1	c.359C>T	p.Thr120Met	missense	Exon 4 of 44	ENSP00000359655.3
EYS	ENST00000393380.6	TSL:1	c.359C>T	p.Thr120Met	missense	Exon 4 of 12	ENSP00000377042.2

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

GnomAD2 exomes

AF:

0.209

AC:

52423

AN:

251270

AF XY:

0.207

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 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

African (AFR)

AF:

0.0364

AC:

1219

AN:

33480

American (AMR)

AF:

0.262

AC:

11720

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

6421

AN:

26134

East Asian (EAS)

AF:

0.254

AC:

10075

AN:

39698

South Asian (SAS)

AF:

0.160

AC:

13826

AN:

86258

European-Finnish (FIN)

AF:

0.220

AC:

11761

AN:

53418

Middle Eastern (MID)

AF:

0.241

AC:

1391

AN:

5768

European-Non Finnish (NFE)

AF:

0.219

AC:

243400

AN:

1111884

Other (OTH)

AF:

0.213

AC:

12837

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

14730

29461

44191

58922

73652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8418

16836

25254

33672

42090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.174

AC:

26538

AN:

152146

Hom.:

2880

Cov.:

AF XY:

0.177

AC XY:

13132

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0400

AC:

1662

AN:

41538

American (AMR)

AF:

0.249

AC:

3811

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

821

AN:

3468

East Asian (EAS)

AF:

0.271

AC:

1398

AN:

5156

South Asian (SAS)

AF:

0.169

AC:

814

AN:

4822

European-Finnish (FIN)

AF:

0.220

AC:

2321

AN:

10568

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14875

AN:

67996

Other (OTH)

AF:

0.220

AC:

464

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1091

2182

3273

4364

5455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.203

Hom.:

11621

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Retinitis pigmentosa (2)

Retinitis pigmentosa 25 (2)

not provided (1)

Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

4.2

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.55

PhyloP100

0.020

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.92

REVEL

Benign

0.13

Sift

Benign

0.19

Sift4G

Uncertain

0.039

Polyphen

0.063

Vest4

0.055

MPC

0.043

ClinPred

0.013

GERP RS

-1.7

Varity_R

0.015

gMVP

0.17

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over