rs782131913

chr11-77181563-G-Achr11-77181563-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_000260.4(MYO7A):c.2878G>A(p.Glu960Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO7A NM_000260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.55

Genes affected

MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 3 uncertain in NM_000260.4
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO7A	NM_000260.4	c.2878G>A	p.Glu960Lys	missense_variant	23/49	ENST00000409709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO7A	ENST00000409709.9	c.2878G>A	p.Glu960Lys	missense_variant	23/49	1	NM_000260.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.42	T;T;.;.;.;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.54	D;D;D;D;D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Uncertain	2.3	M;.;M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.2	N;.;N;N;.;N
REVEL	Uncertain	0.51
Sift	Benign	0.24	T;.;T;T;.;T
Sift4G	Benign	0.26	T;T;T;T;.;T
Polyphen		0.24	B;.;.;.;.;.
Vest4		0.82
MutPred		0.27		Gain of ubiquitination at E960 (P = 0.0039);Gain of ubiquitination at E960 (P = 0.0039);Gain of ubiquitination at E960 (P = 0.0039);.;.;.;
MVP		0.92
MPC		0.31
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.50
gMVP		0.43

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: rs782131913; hg19: chr11-76892609; COSMIC: COSV68683511; COSMIC: COSV68683511;