Genetic Variant NM_001142800.2:c.5705A>C (chr6-64439292-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142800.2(EYS):c.5705A>C(p.Asn1902Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1902I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.304

Publications

23 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.070277244).

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.5705A>C	p.Asn1902Thr	missense	Exon 27 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.5705A>C	p.Asn1902Thr	missense	Exon 27 of 44	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.5705A>C	p.Asn1902Thr	missense	Exon 27 of 43	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.5705A>C	p.Asn1902Thr	missense	Exon 27 of 44	ENSP00000359655.3	Q5T1H1-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1371836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

675592

African (AFR)

AF:

0.00

AC:

AN:

29836

American (AMR)

AF:

0.00

AC:

AN:

31000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24686

East Asian (EAS)

AF:

0.00

AC:

AN:

33840

South Asian (SAS)

AF:

0.00

AC:

AN:

72980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5630

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1067874

Other (OTH)

AF:

0.00

AC:

AN:

56956

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.034

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.46

M_CAP

Benign

0.039

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

0.30

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.66

REVEL

Benign

0.087

Sift

Uncertain

0.025

Sift4G

Uncertain

0.010

Polyphen

0.021

Vest4

0.12

MutPred

0.53

Loss of catalytic residue at P1903 (P = 0.3315)

MVP

0.072

MPC

0.012

ClinPred

0.074

GERP RS

-1.4

Varity_R

0.064

gMVP

0.011

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over