NM_003803.4:c.1112-11T>C

Variant names:

• chr18-3174011-A-G
• rs59555146
• NM_003803.4:c.1112-11T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003803.4(MYOM1):​c.1112-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,612,760 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (37 hom.)
• Consequence: MYOM1 NM_003803.4 intron
• Scores: Splicing: ADA: 0.00004147
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.648
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 18-3174011-A-G is Benign according to our data. Variant chr18-3174011-A-G is described in CliVar as Benign. Clinvar id is 226797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-3174011-A-G is described in CliVar as Benign. Clinvar id is 226797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-3174011-A-G is described in CliVar as Benign. Clinvar id is 226797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-3174011-A-G is described in CliVar as Benign. Clinvar id is 226797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-3174011-A-G is described in CliVar as Benign. Clinvar id is 226797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-3174011-A-G is described in CliVar as Benign. Clinvar id is 226797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-3174011-A-G is described in CliVar as Benign. Clinvar id is 226797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-3174011-A-G is described in CliVar as Benign. Clinvar id is 226797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00158 (241/152276) while in subpopulation EAS AF = 0.0419 (217/5178). AF 95% confidence interval is 0.0373. There are 7 homozygotes in GnomAd4. There are 139 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 241 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM1	NM_003803.4	c.1112-11T>C		intron_variant	Intron 7 of 37	ENST00000356443.9	NP_003794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOM1	ENST00000356443.9	c.1112-11T>C		intron_variant	Intron 7 of 37	1	NM_003803.4	ENSP00000348821.4
MYOM1	ENST00000261606.11	c.1112-11T>C		intron_variant	Intron 7 of 36	1		ENSP00000261606.7

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 240 AN: 152158 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00343 AC: 853 AN: 248742 AF XY: 0.00341

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.0000873

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0428

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.000829

GnomAD4 exome AF: 0.00122 AC: 1787 AN: 1460484 Hom.: 37 Cov.: 33 AF XY: 0.00130 AC XY: 942 AN XY: 726542

African (AFR) AF: 0.0000299 AC: 1 AN: 33408

American (AMR) AF: 0.000112 AC: 5 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0359 AC: 1427 AN: 39698

South Asian (SAS) AF: 0.00187 AC: 161 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.0000990 AC: 110 AN: 1110974

Other (OTH) AF: 0.00129 AC: 78 AN: 60308

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152276 Hom.: 7 Cov.: 32 AF XY: 0.00187 AC XY: 139 AN XY: 74460

African (AFR) AF: 0.0000481 AC: 2 AN: 41556

American (AMR) AF: 0.000196 AC: 3 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0419 AC: 217 AN: 5178

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000247 Hom.: 0

Bravo AF: 0.00209

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

1112-11T>C in intron 7 of MYOM1: This variant is not expected to have clinical s ignificance because it has been identified in 7.2% (14/194) of Han Chinese chrom osomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm. nih.gov/projects/SNP; dbSNP rs59555146). -

Hypertrophic cardiomyopathy Benign:1

Jan 19, 2025

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
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.36
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000041
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs59555146; hg19: chr18-3174009;