rs137975387

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005379.4(MYO1A):ā€‹c.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

Scores

2
10
7

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.39
Variant links:
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 UniProt
MYO1ANM_005379.4 linkuse as main transcriptc.682C>G p.Leu228Val missense_variant 9/28 ENST00000300119.8
MYO1ANM_001256041.2 linkuse as main transcriptc.682C>G p.Leu228Val missense_variant 10/29
MYO1AXM_047428876.1 linkuse as main transcriptc.682C>G p.Leu228Val missense_variant 10/29
MYO1AXM_011538373.3 linkuse as main transcriptc.682C>G p.Leu228Val missense_variant 9/25

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYO1AENST00000300119.8 linkuse as main transcriptc.682C>G p.Leu228Val missense_variant 9/281 NM_005379.4 P1
MYO1AENST00000442789.6 linkuse as main transcriptc.682C>G p.Leu228Val missense_variant 10/291 P1
MYO1AENST00000492945.5 linkuse as main transcriptc.-20-810C>G intron_variant 4
MYO1AENST00000554234.5 linkuse as main transcriptc.196C>G p.Leu66Val missense_variant, NMD_transcript_variant 5/245

Frequencies

GnomAD3 genomes
AF:
0.00113
AC:
172
AN:
152214
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00400
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000314
AC:
79
AN:
251334
Hom.:
0
AF XY:
0.000213
AC XY:
29
AN XY:
135852
show subpopulations
Gnomad AFR exome
AF:
0.00443
Gnomad AMR exome
AF:
0.000173
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000117
AC:
171
AN:
1461838
Hom.:
0
Cov.:
32
AF XY:
0.000103
AC XY:
75
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00433
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.00113
AC:
172
AN:
152332
Hom.:
0
Cov.:
32
AF XY:
0.00111
AC XY:
83
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.00399
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000271
Hom.:
0
Bravo
AF:
0.00125
ESP6500AA
AF:
0.00522
AC:
23
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000412
AC:
50

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 submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineFeb 18, 2015p.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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.55
D;D
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.74
.;T
M_CAP
Uncertain
0.16
D
MetaRNN
Benign
0.041
T;T
MetaSVM
Uncertain
0.50
D
MutationAssessor
Uncertain
2.5
M;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-2.3
N;N
REVEL
Pathogenic
0.66
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
1.0
D;D
Vest4
0.57
MVP
0.85
MPC
0.43
ClinPred
0.14
T
GERP RS
3.0
Varity_R
0.60
gMVP
0.52

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: rs137975387; hg19: chr12-57437952; API