rs6506073

Variant names:

• chr18-3156063-G-A
• rs6506073
• NM_003803.4:c.1502-975C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003803.4(MYOM1):​c.1502-975C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,102 control chromosomes in the GnomAD database, including 6,534 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6534 hom., cov: 32)
• Consequence: MYOM1 NM_003803.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003803.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM1	NM_003803.4	MANE Select	c.1502-975C>T		intron	N/A	NP_003794.3
	MYOM1	NM_019856.2		c.1502-975C>T		intron	N/A	NP_062830.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM1	ENST00000356443.9	TSL:1 MANE Select	c.1502-975C>T		intron	N/A	ENSP00000348821.4
	MYOM1	ENST00000261606.11	TSL:1	c.1502-975C>T		intron	N/A	ENSP00000261606.7

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42288 AN: 151982 Hom.: 6510 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 42360 AN: 152102 Hom.: 6534 Cov.: 32 AF XY: 0.274 AC XY: 20374 AN XY: 74376

African (AFR) AF: 0.416 AC: 17251 AN: 41460

American (AMR) AF: 0.231 AC: 3527 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3468

East Asian (EAS) AF: 0.284 AC: 1474 AN: 5182

South Asian (SAS) AF: 0.309 AC: 1491 AN: 4828

European-Finnish (FIN) AF: 0.163 AC: 1723 AN: 10600

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14985 AN: 67984

Other (OTH) AF: 0.303 AC: 639 AN: 2112

Alfa AF: 0.238 Hom.: 5878

Bravo AF: 0.288

Asia WGS AF: 0.311 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.33
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6506073; hg19: chr18-3156061;