12-57036985-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_005379.4(MYO1A):c.2162G>A(p.Arg721Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,614,174 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
MYO1A
NM_005379.4 missense
NM_005379.4 missense
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: 1.22
Genes affected
MYO1A (HGNC:7595): (myosin IA) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional skeletal muscle myosin-1 (MYH1). Unconventional myosins contain the basic domains characteristic of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with autosomal dominant deafness. Alternatively spliced variants have been found for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP6
Variant 12-57036985-C-T is Benign according to our data. Variant chr12-57036985-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 227657.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO1A | NM_005379.4 | c.2162G>A | p.Arg721Gln | missense_variant | 20/28 | ENST00000300119.8 | |
MYO1A | NM_001256041.2 | c.2162G>A | p.Arg721Gln | missense_variant | 21/29 | ||
MYO1A | XM_047428876.1 | c.2162G>A | p.Arg721Gln | missense_variant | 21/29 | ||
MYO1A | XM_011538373.3 | c.2162G>A | p.Arg721Gln | missense_variant | 20/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO1A | ENST00000300119.8 | c.2162G>A | p.Arg721Gln | missense_variant | 20/28 | 1 | NM_005379.4 | P1 | |
MYO1A | ENST00000442789.6 | c.2162G>A | p.Arg721Gln | missense_variant | 21/29 | 1 | P1 | ||
MYO1A | ENST00000554234.5 | c.1676G>A | p.Arg559Gln | missense_variant, NMD_transcript_variant | 16/24 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251442Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135888
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461892Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11AN XY: 727248
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74452
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
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 02, 2015 | p.Arg721Gln in exon 20 of MYO1A: This variant is not expected to have clinical s ignificance to hearing loss because recent evidence has disqualified an associat ion between variants in the MYO1A gene and hearing loss (Eisenberger 2014). Thi s variant has also been identified in 2/67702 of European chromosomes and 1/166 26 South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs138855953). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
0.23
ClinPred
T
GERP RS
Varity_R
gMVP
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