rs779385322

Variant names:

• chr6-133382417-A-C
• rs779385322
• NM_004100.5:c.59A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-133382417-A-C
• chr6-133382417-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004100.5(EYA4):​c.59A>C​(p.Asp20Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 32)
• Consequence: EYA4 NM_004100.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.42

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2908938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYA4	NM_004100.5	c.59A>C	p.Asp20Ala	missense_variant	Exon 3 of 20	ENST00000355286.12	NP_004091.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYA4	ENST00000355286.12	c.59A>C	p.Asp20Ala	missense_variant	Exon 3 of 20	1	NM_004100.5	ENSP00000347434.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0094	.;T;T;.;T;.;T;T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T;T;.;T;T;D;T;D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.29	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.041	T
MutationAssessor	Benign	0.34	N;.;N;N;N;N;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.76	N;N;N;N;N;N;N;N
REVEL	Uncertain	0.45
Sift	Benign	0.11	T;T;D;D;D;D;D;D
Sift4G	Benign	0.30	T;T;T;T;T;T;T;T
Polyphen		1.0, 0.0, 0.0010, 0.034	.;D;B;B;B;D;B;.
Vest4		0.37
MutPred		0.060		Gain of MoRF binding (P = 0.1235);Gain of MoRF binding (P = 0.1235);Gain of MoRF binding (P = 0.1235);Gain of MoRF binding (P = 0.1235);Gain of MoRF binding (P = 0.1235);Gain of MoRF binding (P = 0.1235);Gain of MoRF binding (P = 0.1235);Gain of MoRF binding (P = 0.1235);
MVP		0.87
MPC		0.19
ClinPred		0.87	D
GERP RS		5.9
Varity_R		0.14
gMVP		0.32

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

Other links and lift over

dbSNP: rs779385322; hg19: chr6-133703555;