chr6-63720604-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001142800.2(EYS):​c.9427G>T​(p.Val3143Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,324,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

2
2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.629
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]
PHF3 (HGNC:8921): (PHD finger protein 3) This gene encodes a member of a PHD finger-containing gene family. This gene may function as a transcription factor and may be involved in glioblastomas development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1
In a domain Laminin G-like 5 (size 190) in uniprot entity EYS_HUMAN there are 14 pathogenic changes around while only 2 benign (88%) in NM_001142800.2
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.071231365).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EYSNM_001142800.2 linkc.9427G>T p.Val3143Phe missense_variant Exon 43 of 43 ENST00000503581.6 NP_001136272.1 Q5T1H1-1
PHF3NM_001370348.2 linkc.*6896C>A 3_prime_UTR_variant Exon 16 of 16 ENST00000262043.8 NP_001357277.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EYSENST00000503581.6 linkc.9427G>T p.Val3143Phe missense_variant Exon 43 of 43 5 NM_001142800.2 ENSP00000424243.1 Q5T1H1-1
EYSENST00000370621.7 linkc.9490G>T p.Val3164Phe missense_variant Exon 44 of 44 1 ENSP00000359655.3 Q5T1H1-3
PHF3ENST00000262043.8 linkc.*6896C>A 3_prime_UTR_variant Exon 16 of 16 5 NM_001370348.2 ENSP00000262043.4 Q92576-1
PHF3ENST00000505138.1 linkc.361+9242C>A intron_variant Intron 3 of 4 3 ENSP00000421417.1 H0Y8L0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000151
AC:
2
AN:
1324566
Hom.:
0
Cov.:
28
AF XY:
0.00000154
AC XY:
1
AN XY:
648114
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000192
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.050
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
12
DANN
Uncertain
0.98
DEOGEN2
Benign
0.042
.;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.47
T;T
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.071
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.69
.;N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.79
N;N
REVEL
Benign
0.26
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.017
B;B
Vest4
0.24
MutPred
0.13
.;Gain of solvent accessibility (P = 0.1185);
MVP
0.14
MPC
0.014
ClinPred
0.078
T
GERP RS
-3.5
Varity_R
0.19
gMVP
0.70

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.

Other links and lift over

dbSNP: rs1038659994; hg19: chr6-64430500; COSMIC: COSV65502873; API