rs9960004

Variant names:

• chr18-3152452-A-G
• rs9960004
• NM_003803.4:c.1644-559T>C

Variant summary

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

The NM_003803.4(MYOM1):​c.1644-559T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,018 control chromosomes in the GnomAD database, including 16,600 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 0.46 (16600 hom., cov: 31)
• Consequence: MYOM1 NM_003803.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 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.1644-559T>C		intron	N/A	NP_003794.3
	MYOM1	NM_019856.2		c.1644-559T>C		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.1644-559T>C		intron	N/A	ENSP00000348821.4
	MYOM1	ENST00000261606.11	TSL:1	c.1644-559T>C		intron	N/A	ENSP00000261606.7

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70328 AN: 151900 Hom.: 16581 Cov.: 31

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.463 AC: 70396 AN: 152018 Hom.: 16600 Cov.: 31 AF XY: 0.453 AC XY: 33663 AN XY: 74330

African (AFR) AF: 0.528 AC: 21872 AN: 41432

American (AMR) AF: 0.422 AC: 6435 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3470

East Asian (EAS) AF: 0.268 AC: 1386 AN: 5172

South Asian (SAS) AF: 0.458 AC: 2209 AN: 4824

European-Finnish (FIN) AF: 0.336 AC: 3548 AN: 10574

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31871 AN: 67970

Other (OTH) AF: 0.470 AC: 992 AN: 2110

Alfa AF: 0.466 Hom.: 21349

Bravo AF: 0.468

Asia WGS AF: 0.364 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.63
PhyloP100		1.7
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: rs9960004; hg19: chr18-3152450;