chr6-133513032-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004100.5(EYA4):āc.1495G>Cā(p.Val499Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
EYA4
NM_004100.5 missense
NM_004100.5 missense
Scores
2
10
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.60
Genes affected
EYA4 (HGNC:3522): (EYA transcriptional coactivator and phosphatase 4) This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator through its protein phosphatase activity, and it may be important for eye development, and for continued function of the mature organ of Corti. Mutations in this gene are associated with postlingual, progressive, autosomal dominant hearing loss at the deafness, autosomal dominant non-syndromic sensorineural 10 locus. The encoded protein is also a putative oncogene that mediates DNA repair, apoptosis, and innate immunity following DNA damage, cellular damage, and viral attack. Defects in this gene are also associated with dilated cardiomyopathy 1J. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251176Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135790
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461586Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727110
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;D;.;D;.;D;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;L;L;L;.;.;.
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
D;D;D;D;.;.;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;T;T;.;.;T;D
Sift4G
Uncertain
D;D;D;D;.;.;D;D
Polyphen
0.35, 0.010, 0.074, 0.088
.;B;B;B;B;B;B;.
Vest4
MutPred
0.49
.;.;.;.;.;.;Loss of MoRF binding (P = 0.094);.;
MVP
MPC
0.18
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at