rs11659820

Variant names:

• chr18-3164387-C-T
• rs11659820
• NM_003803.4:c.1392G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003803.4(MYOM1):​c.1392G>A​(p.Arg464Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,609,800 control chromosomes in the GnomAD database, including 35,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3510 hom., cov: 33)
  • Exomes 𝑓: 0.20 (31905 hom.)
• Consequence: MYOM1 NM_003803.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.573
• Publications: 10 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 18-3164387-C-T is Benign according to our data. Variant chr18-3164387-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.573 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM1	NM_003803.4	MANE Select	c.1392G>A	p.Arg464Arg	synonymous	Exon 10 of 38	NP_003794.3
	MYOM1	NM_019856.2		c.1392G>A	p.Arg464Arg	synonymous	Exon 10 of 37	NP_062830.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM1	ENST00000356443.9	TSL:1 MANE Select	c.1392G>A	p.Arg464Arg	synonymous	Exon 10 of 38	ENSP00000348821.4
	MYOM1	ENST00000261606.11	TSL:1	c.1392G>A	p.Arg464Arg	synonymous	Exon 10 of 37	ENSP00000261606.7
	MYOM1	ENST00000941943.1		c.1392G>A	p.Arg464Arg	synonymous	Exon 10 of 38	ENSP00000612002.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31880 AN: 152084 Hom.: 3497 Cov.: 33

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.216

GnomAD2 exomes AF: 0.180 AC: 43521 AN: 242424 AF XY: 0.181

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.191

Gnomad EAS exome AF: 0.00534

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.204 AC: 296877 AN: 1457598 Hom.: 31905 Cov.: 33 AF XY: 0.203 AC XY: 147231 AN XY: 724694

African (AFR) AF: 0.270 AC: 9036 AN: 33438

American (AMR) AF: 0.157 AC: 6935 AN: 44112

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4968 AN: 26012

East Asian (EAS) AF: 0.00449 AC: 178 AN: 39642

South Asian (SAS) AF: 0.180 AC: 15376 AN: 85492

European-Finnish (FIN) AF: 0.149 AC: 7932 AN: 53240

Middle Eastern (MID) AF: 0.209 AC: 1205 AN: 5764

European-Non Finnish (NFE) AF: 0.216 AC: 239670 AN: 1109618

Other (OTH) AF: 0.192 AC: 11577 AN: 60280

GnomAD4 genome AF: 0.210 AC: 31929 AN: 152202 Hom.: 3510 Cov.: 33 AF XY: 0.205 AC XY: 15221 AN XY: 74430

African (AFR) AF: 0.267 AC: 11069 AN: 41510

American (AMR) AF: 0.192 AC: 2930 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 683 AN: 3472

East Asian (EAS) AF: 0.00520 AC: 27 AN: 5194

South Asian (SAS) AF: 0.171 AC: 826 AN: 4818

European-Finnish (FIN) AF: 0.138 AC: 1467 AN: 10596

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14126 AN: 68002

Other (OTH) AF: 0.214 AC: 452 AN: 2116

Alfa AF: 0.212 Hom.: 2327

Bravo AF: 0.216

Asia WGS AF: 0.102 AC: 357 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	8.8
DANN	Benign	0.59
PhyloP100		0.57
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: rs11659820; hg19: chr18-3164385; COSMIC: COSV55302241;