rs137975387
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_005379.4(MYO1A):āc.682C>Gā(p.Leu228Val) variant causes a missense change. The variant allele was found at a frequency of 0.000212 in 1,614,170 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 Benign (ā ).
Frequency
Genomes: š 0.0011 ( 0 hom., cov: 32)
Exomes š: 0.00012 ( 0 hom. )
Consequence
MYO1A
NM_005379.4 missense
NM_005379.4 missense
Scores
2
10
7
Clinical Significance
Conservation
PhyloP100: 6.39
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 Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.040592015).
BP6
Variant 12-57044168-G-C is Benign according to our data. Variant chr12-57044168-G-C is described in ClinVar as [Benign]. Clinvar id is 226794.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 172 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYO1A | NM_005379.4 | c.682C>G | p.Leu228Val | missense_variant | 9/28 | ENST00000300119.8 | NP_005370.1 | |
MYO1A | NM_001256041.2 | c.682C>G | p.Leu228Val | missense_variant | 10/29 | NP_001242970.1 | ||
MYO1A | XM_047428876.1 | c.682C>G | p.Leu228Val | missense_variant | 10/29 | XP_047284832.1 | ||
MYO1A | XM_011538373.3 | c.682C>G | p.Leu228Val | missense_variant | 9/25 | XP_011536675.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO1A | ENST00000300119.8 | c.682C>G | p.Leu228Val | missense_variant | 9/28 | 1 | NM_005379.4 | ENSP00000300119.3 | ||
MYO1A | ENST00000442789.6 | c.682C>G | p.Leu228Val | missense_variant | 10/29 | 1 | ENSP00000393392.2 | |||
MYO1A | ENST00000492945.5 | c.-20-810C>G | intron_variant | 4 | ENSP00000452229.1 | |||||
MYO1A | ENST00000554234.5 | n.196C>G | non_coding_transcript_exon_variant | 5/24 | 5 | ENSP00000451033.1 |
Frequencies
GnomAD3 genomes AF: 0.00113 AC: 172AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000314 AC: 79AN: 251334Hom.: 0 AF XY: 0.000213 AC XY: 29AN XY: 135852
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GnomAD4 exome AF: 0.000117 AC: 171AN: 1461838Hom.: 0 Cov.: 32 AF XY: 0.000103 AC XY: 75AN XY: 727224
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GnomAD4 genome AF: 0.00113 AC: 172AN: 152332Hom.: 0 Cov.: 32 AF XY: 0.00111 AC XY: 83AN XY: 74480
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 18, 2015 | p.Leu228Val in exon 9 of MYO1A: This variant is not expected to have clinical si gnificance because it has been identified in 0.4% (46/10402) of African chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs137975387). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
0.43
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