11-77177597-G-C

Variant summary

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

The NM_000260.4(MYO7A):​c.2236G>C​(p.Asp746His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D746N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

MYO7A
NM_000260.4 missense

Scores

2
12
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.54
Variant links:
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]

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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

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYO7ANM_000260.4 linkuse as main transcriptc.2236G>C p.Asp746His missense_variant 19/49 ENST00000409709.9 NP_000251.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYO7AENST00000409709.9 linkuse as main transcriptc.2236G>C p.Asp746His missense_variant 19/491 NM_000260.4 ENSP00000386331 Q13402-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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
0.24
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.70
D;T;.;.;.
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.96
D;D;D;D;D
M_CAP
Uncertain
0.086
D
MetaRNN
Uncertain
0.54
D;D;D;D;D
MetaSVM
Uncertain
-0.25
T
MutationAssessor
Benign
1.9
L;.;L;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.1
D;.;D;D;.
REVEL
Uncertain
0.36
Sift
Benign
0.17
T;.;T;T;.
Sift4G
Benign
0.22
T;T;T;T;.
Polyphen
1.0
D;.;.;.;.
Vest4
0.72
MutPred
0.30
Gain of MoRF binding (P = 0.0633);Gain of MoRF binding (P = 0.0633);Gain of MoRF binding (P = 0.0633);.;.;
MVP
0.87
MPC
0.46
ClinPred
0.98
D
GERP RS
5.0
Varity_R
0.51
gMVP
0.72

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: rs36090425; hg19: chr11-76888643; API