6-133513032-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004100.5(EYA4):ā€‹c.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

Scores

2
10
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.60
Variant links:
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]
TARID (HGNC:50506): (TCF21 antisense RNA inducing promoter demethylation)

Genome browser will be placed here

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

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EYA4NM_004100.5 linkc.1495G>C p.Val499Leu missense_variant 16/20 ENST00000355286.12 NP_004091.3 O95677-1Q96CJ7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EYA4ENST00000355286.12 linkc.1495G>C p.Val499Leu missense_variant 16/201 NM_004100.5 ENSP00000347434.7 O95677-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251176
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135790
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461586
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727110
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:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.69
BayesDel_addAF
Uncertain
0.077
D
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.097
.;T;D;.;D;.;D;T
Eigen
Benign
-0.056
Eigen_PC
Benign
0.074
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.97
D;D;.;D;D;D;D;D
M_CAP
Benign
0.085
D
MetaRNN
Uncertain
0.51
D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.28
T
MutationAssessor
Benign
1.7
.;.;L;L;L;.;.;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-2.8
D;D;D;D;.;.;D;D
REVEL
Uncertain
0.54
Sift
Uncertain
0.0010
D;D;T;T;.;.;T;D
Sift4G
Uncertain
0.0030
D;D;D;D;.;.;D;D
Polyphen
0.35, 0.010, 0.074, 0.088
.;B;B;B;B;B;B;.
Vest4
0.48
MutPred
0.49
.;.;.;.;.;.;Loss of MoRF binding (P = 0.094);.;
MVP
0.77
MPC
0.18
ClinPred
0.59
D
GERP RS
4.7
Varity_R
0.21
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs142122118; hg19: chr6-133834170; API