6-64626200-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001142800.2(EYS):c.3489T>A(p.Asn1163Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,534,824 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. N1163N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:3

Conservation

PhyloP100: 2.40

Publications

9 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0090017915).

BP6

Variant 6-64626200-A-T is Benign according to our data. Variant chr6-64626200-A-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 143102.

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.3489T>A	p.Asn1163Lys	missense	Exon 23 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.3489T>A	p.Asn1163Lys	missense	Exon 23 of 44	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EYS	ENST00000503581.6	TSL:5 MANE Select	c.3489T>A	p.Asn1163Lys	missense	Exon 23 of 43	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7	TSL:1	c.3489T>A	p.Asn1163Lys	missense	Exon 23 of 44	ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000330816.5	TSL:3	n.110T>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00847

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000710

AC:

AN:

136712

AF XY:

0.000650

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00851

Gnomad FIN exome

AF:

0.0000664

Gnomad NFE exome

AF:

0.0000541

Gnomad OTH exome

AF:

0.000252

GnomAD4 exome

AF:

0.000297

AC:

411

AN:

1382514

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

222

AN XY:

681140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30692

American (AMR)

AF:

0.00

AC:

AN:

30762

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24680

East Asian (EAS)

AF:

0.00737

AC:

262

AN:

35564

South Asian (SAS)

AF:

0.00105

AC:

AN:

74258

European-Finnish (FIN)

AF:

0.0000407

AC:

AN:

49194

Middle Eastern (MID)

AF:

0.00130

AC:

AN:

5386

European-Non Finnish (NFE)

AF:

0.0000298

AC:

AN:

1074546

Other (OTH)

AF:

0.000522

AC:

AN:

57432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000355

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41562

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00849

AC:

AN:

5184

South Asian (SAS)

AF:

0.00145

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000284

Hom.:

Bravo

AF:

0.000502

ExAC

AF:

0.000329

AC:

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Retinitis pigmentosa 25 (2)

EYS-related disorder (1)

Retinal dystrophy (1)

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.0090

MetaSVM

Uncertain

0.59

MutationAssessor

Uncertain

2.1

PhyloP100

2.4

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.7

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

0.94

Vest4

0.33

MutPred

0.56

Gain of ubiquitination at N1163 (P = 0.0162)

MVP

0.52

MPC

0.061

ClinPred

0.12

GERP RS

3.0

Varity_R

0.26

gMVP

0.45

Mutation Taster

=50/50

(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

Computational scores

Splicing

Publications

Other links and lift over