rs751242817
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000260.4(MYO7A):c.4650G>A(p.Pro1550=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000053 in 1,604,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000052 ( 0 hom. )
Consequence
MYO7A
NM_000260.4 synonymous
NM_000260.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.340
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 Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 11-77199616-G-A is Benign according to our data. Variant chr11-77199616-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.34 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.4650G>A | p.Pro1550= | synonymous_variant | 35/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.4650G>A | p.Pro1550= | synonymous_variant | 35/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152242Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000344 AC: 8AN: 232824Hom.: 0 AF XY: 0.0000315 AC XY: 4AN XY: 126958
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GnomAD4 exome AF: 0.0000516 AC: 75AN: 1452358Hom.: 0 Cov.: 30 AF XY: 0.0000582 AC XY: 42AN XY: 721376
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74380
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 12, 2015 | p.Pro1550Pro in exon 35 of MYO7A: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 2/30922 of Europ ean (non-Finnish) chromosomes and 1/4450 of African chromosomes by the Exome Agg regation Consortium (ExAC, http://exac.broadinstitute.org). - |
MYO7A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 22, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at