rs36098676

Variant names:

• chr18-3149155-C-T
• rs36098676
• NM_003803.4:c.1890G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-3149155-C-T
• chr18-3149155-C-A

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.1890G>A​(p.Glu630Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,613,614 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (44 hom.)
• Consequence: MYOM1 NM_003803.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.256
• Publications: 2 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=-0.47).
• BP6: Variant 18-3149155-C-T is Benign according to our data. Variant chr18-3149155-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00538 (819/152268) while in subpopulation AFR AF = 0.017 (706/41554). AF 95% confidence interval is 0.016. There are 7 homozygotes in GnomAd4. There are 380 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 819 AD gene.

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.1890G>A	p.Glu630Glu	synonymous	Exon 13 of 38	NP_003794.3
	MYOM1	NM_019856.2		c.1890G>A	p.Glu630Glu	synonymous	Exon 13 of 37	NP_062830.1	P52179-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM1	ENST00000356443.9	TSL:1 MANE Select	c.1890G>A	p.Glu630Glu	synonymous	Exon 13 of 38	ENSP00000348821.4	P52179-1
	MYOM1	ENST00000261606.11	TSL:1	c.1890G>A	p.Glu630Glu	synonymous	Exon 13 of 37	ENSP00000261606.7	P52179-2
	MYOM1	ENST00000941943.1		c.1890G>A	p.Glu630Glu	synonymous	Exon 13 of 38	ENSP00000612002.1

Frequencies

GnomAD3 genomes AF: 0.00532 AC: 810 AN: 152150 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00344 AC: 858 AN: 249224 AF XY: 0.00384

Gnomad AFR exome AF: 0.0163

Gnomad AMR exome AF: 0.000637

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00169 AC: 2475 AN: 1461346 Hom.: 44 Cov.: 30 AF XY: 0.00212 AC XY: 1540 AN XY: 726940

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0180 AC: 603 AN: 33456

American (AMR) AF: 0.000760 AC: 34 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39694

South Asian (SAS) AF: 0.0178 AC: 1532 AN: 86138

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53396

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.0000945 AC: 105 AN: 1111682

Other (OTH) AF: 0.00297 AC: 179 AN: 60356

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00538 AC: 819 AN: 152268 Hom.: 7 Cov.: 31 AF XY: 0.00510 AC XY: 380 AN XY: 74444

African (AFR) AF: 0.0170 AC: 706 AN: 41554

American (AMR) AF: 0.00163 AC: 25 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00259 Hom.: 0

Bravo AF: 0.00524

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Hypertrophic cardiomyopathy (1)
-	-	1	MYOM1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.1
DANN	Benign	0.67
PhyloP100		0.26
Mutation Taster		=90/10	polymorphism

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: rs36098676; hg19: chr18-3149153;