rs61753849

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PP3_StrongBS2

The NM_005379.4(MYO1A):​c.1155G>T​(p.Glu385Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,613,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E385V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

MYO1A
NM_005379.4 missense

Scores

10
8
1

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.554

Publications

15 publications found
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]
MYO1A Gene-Disease associations (from GenCC):
  • nonsyndromic genetic hearing loss
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.948
BS2
High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO1ANM_005379.4 linkc.1155G>T p.Glu385Asp missense_variant Exon 13 of 28 ENST00000300119.8 NP_005370.1 Q9UBC5
MYO1ANM_001256041.2 linkc.1155G>T p.Glu385Asp missense_variant Exon 14 of 29 NP_001242970.1 Q9UBC5B2R643
MYO1AXM_047428876.1 linkc.1155G>T p.Glu385Asp missense_variant Exon 14 of 29 XP_047284832.1
MYO1AXM_011538373.3 linkc.1155G>T p.Glu385Asp missense_variant Exon 13 of 25 XP_011536675.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYO1AENST00000300119.8 linkc.1155G>T p.Glu385Asp missense_variant Exon 13 of 28 1 NM_005379.4 ENSP00000300119.3 Q9UBC5
MYO1AENST00000442789.6 linkc.1155G>T p.Glu385Asp missense_variant Exon 14 of 29 1 ENSP00000393392.2 Q9UBC5
MYO1AENST00000554234.5 linkn.669G>T non_coding_transcript_exon_variant Exon 9 of 24 5 ENSP00000451033.1 G3V342
MYO1AENST00000492945.5 linkc.*22G>T downstream_gene_variant 4 ENSP00000452229.1 G3V587

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000176
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.000107
AC:
27
AN:
251450
AF XY:
0.0000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000229
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000111
AC:
162
AN:
1461308
Hom.:
0
Cov.:
31
AF XY:
0.000109
AC XY:
79
AN XY:
726998
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33454
American (AMR)
AF:
0.00
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86238
European-Finnish (FIN)
AF:
0.0000187
AC:
1
AN:
53414
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.000137
AC:
152
AN:
1111504
Other (OTH)
AF:
0.000149
AC:
9
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.471
Heterozygous variant carriers
0
9
17
26
34
43
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74310
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41410
American (AMR)
AF:
0.0000655
AC:
1
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5196
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000176
AC:
12
AN:
68032
Other (OTH)
AF:
0.000478
AC:
1
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000196
Hom.:
0
Bravo
AF:
0.000106
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 48 Uncertain:1
May 01, 2014
OMIM
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Pathogenic
0.29
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.85
D;D
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Pathogenic
0.99
.;D
M_CAP
Uncertain
0.25
D
MetaRNN
Pathogenic
0.95
D;D
MetaSVM
Uncertain
0.52
D
MutationAssessor
Pathogenic
4.5
H;H
PhyloP100
0.55
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.0
D;D
REVEL
Pathogenic
0.80
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.88
MutPred
0.95
Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);
MVP
0.91
MPC
0.44
ClinPred
0.96
D
GERP RS
2.2
Varity_R
0.91
gMVP
0.69
Mutation Taster
=60/40
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
Splicevardb
2.0
SpliceAI score (max)
0.12
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs61753849; hg19: chr12-57435225; API