NM_003803.4:c.290G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP3BP6_Very_StrongBS2

The NM_003803.4(MYOM1):​c.290G>T​(p.Gly97Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000874 in 1,592,304 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G97R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00040 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00092 ( 21 hom. )

Consequence

MYOM1
NM_003803.4 missense, splice_region

Scores

5
13
Splicing: ADA: 0.9996
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.50

Publications

2 publications found
Variant links:
Genes affected
MYOM1 (HGNC:7613): (myomesin 1) The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD (myomesin 1) and 165 kD (myomesin 2). This protein, myomesin 1, like myomesin 2, titin, and other myofibrillar proteins contains structural modules with strong homology to either fibronectin type III (motif I) or immunoglobulin C2 (motif II) domains. Myomesin 1 and myomesin 2 each have a unique N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the titin string extends into the center of the M band. The integrating structure of the sarcomere arises from muscle-specific members of the superfamily of immunoglobulin-like proteins. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
MYOM1 Gene-Disease associations (from GenCC):
  • hypertrophic cardiomyopathy
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

PP3
Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
Variant 18-3214934-C-A is Benign according to our data. Variant chr18-3214934-C-A is described in ClinVar as [Benign]. Clinvar id is 226817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 61 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYOM1NM_003803.4 linkc.290G>T p.Gly97Val missense_variant, splice_region_variant Exon 2 of 38 ENST00000356443.9 NP_003794.3 P52179-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYOM1ENST00000356443.9 linkc.290G>T p.Gly97Val missense_variant, splice_region_variant Exon 2 of 38 1 NM_003803.4 ENSP00000348821.4 P52179-1
MYOM1ENST00000261606.11 linkc.290G>T p.Gly97Val missense_variant, splice_region_variant Exon 2 of 37 1 ENSP00000261606.7 P52179-2
ENSG00000265399ENST00000580139.1 linkn.198-2058C>A intron_variant Intron 2 of 4 2

Frequencies

GnomAD3 genomes
AF:
0.000401
AC:
61
AN:
152194
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00198
AC:
462
AN:
233542
AF XY:
0.00276
show subpopulations
Gnomad AFR exome
AF:
0.0000658
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:
0.00
Gnomad OTH exome
AF:
0.00158
GnomAD4 exome
AF:
0.000924
AC:
1331
AN:
1439992
Hom.:
21
Cov.:
33
AF XY:
0.00138
AC XY:
987
AN XY:
713358
show subpopulations
African (AFR)
AF:
0.0000302
AC:
1
AN:
33080
American (AMR)
AF:
0.00
AC:
0
AN:
43672
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24760
East Asian (EAS)
AF:
0.0000254
AC:
1
AN:
39362
South Asian (SAS)
AF:
0.0152
AC:
1272
AN:
83474
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52068
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4928
European-Non Finnish (NFE)
AF:
0.00000455
AC:
5
AN:
1099346
Other (OTH)
AF:
0.000877
AC:
52
AN:
59302
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
67
134
201
268
335
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.000400
AC:
61
AN:
152312
Hom.:
1
Cov.:
32
AF XY:
0.000564
AC XY:
42
AN XY:
74472
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41574
American (AMR)
AF:
0.00
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5178
South Asian (SAS)
AF:
0.0124
AC:
60
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68038
Other (OTH)
AF:
0.00
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
3
6
9
12
15
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
4
8
12
16
20
<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:
0.000111
Hom.:
1
Bravo
AF:
0.0000680
ExAC
AF:
0.00214
AC:
259
Asia WGS
AF:
0.00462
AC:
16
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Jun 11, 2015
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

p.Gly97Val in exon 2 of MYOM1: This variant is not expected to have clinical sig nificance because it has been identified in 2.1% (228/10648) of South Asian chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs568600892). -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Hypertrophic cardiomyopathy Benign:1
Dec 30, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.032
T;.
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.77
T;T
MetaRNN
Benign
0.0080
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
2.0
M;M
PhyloP100
2.5
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.095
Sift
Uncertain
0.0030
D;D
Sift4G
Benign
0.26
T;T
Polyphen
0.68
P;P
Vest4
0.57
MutPred
0.17
Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);
MVP
0.85
MPC
0.17
ClinPred
0.047
T
GERP RS
5.6
Varity_R
0.20
gMVP
0.54
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.92
SpliceAI score (max)
0.74
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.74
Position offset: 0

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

Publications

Other links and lift over

dbSNP: rs568600892; hg19: chr18-3214932; API