11-77156022-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong

The NM_000260.4(MYO7A):​c.401T>C​(p.Ile134Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I134N) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Consequence

MYO7A
NM_000260.4 missense

Scores

14
4
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00
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 Likely_pathogenic. Variant got 8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr11-77156022-T-A is described in Lovd as [Likely_pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.981

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO7ANM_000260.4 linkc.401T>C p.Ile134Thr missense_variant Exon 5 of 49 ENST00000409709.9 NP_000251.3 Q13402-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYO7AENST00000409709.9 linkc.401T>C p.Ile134Thr missense_variant Exon 5 of 49 1 NM_000260.4 ENSP00000386331.3 Q13402-1
MYO7AENST00000458637.6 linkc.401T>C p.Ile134Thr missense_variant Exon 5 of 49 1 ENSP00000392185.2 Q13402-2
MYO7AENST00000409619.6 linkc.368T>C p.Ile123Thr missense_variant Exon 6 of 50 1 ENSP00000386635.2 Q13402-8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Sep 10, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Pathogenic
0.46
D
BayesDel_noAF
Pathogenic
0.43
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.91
D;T;.;.
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Pathogenic
0.63
D
MetaRNN
Pathogenic
0.98
D;D;D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
3.1
M;.;M;.
PrimateAI
Pathogenic
0.88
D
PROVEAN
Uncertain
-3.9
D;.;D;D
REVEL
Pathogenic
0.94
Sift
Uncertain
0.0010
D;.;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D
Polyphen
0.73
P;.;.;.
Vest4
0.94
MutPred
0.88
Gain of disorder (P = 0.0391);Gain of disorder (P = 0.0391);Gain of disorder (P = 0.0391);.;
MVP
0.96
MPC
0.23
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.76
gMVP
0.82

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs111033181; hg19: chr11-76867068; API