18-3116343-G-A

Variant names:

• chr18-3116343-G-A
• rs201092091
• NM_003803.4:c.3291C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003803.4(MYOM1):​c.3291C>T​(p.Asn1097Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00098 in 1,611,152 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (2 hom.)
• Consequence: MYOM1 NM_003803.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.850
• Publications: 0 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 18-3116343-G-A is Benign according to our data. Variant chr18-3116343-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 416027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.85 with no splicing effect.
• BS2: High AC in GnomAd4 at 75 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.3291C>T	p.Asn1097Asn	synonymous	Exon 21 of 38	NP_003794.3
	MYOM1	NM_019856.2		c.3003C>T	p.Asn1001Asn	synonymous	Exon 20 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.3291C>T	p.Asn1097Asn	synonymous	Exon 21 of 38	ENSP00000348821.4	P52179-1
	MYOM1	ENST00000261606.11	TSL:1	c.3003C>T	p.Asn1001Asn	synonymous	Exon 20 of 37	ENSP00000261606.7	P52179-2
	MYOM1	ENST00000941943.1		c.3255C>T	p.Asn1085Asn	synonymous	Exon 21 of 38	ENSP00000612002.1

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 75 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000385 AC: 95 AN: 246554 AF XY: 0.000441

Gnomad AFR exome AF: 0.000392

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000561

Gnomad FIN exome AF: 0.000374

Gnomad NFE exome AF: 0.000672

Gnomad OTH exome AF: 0.000667

GnomAD4 exome AF: 0.00103 AC: 1504 AN: 1458986 Hom.: 2 Cov.: 30 AF XY: 0.00103 AC XY: 747 AN XY: 725672

African (AFR) AF: 0.000240 AC: 8 AN: 33402

American (AMR) AF: 0.0000224 AC: 1 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39676

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85906

European-Finnish (FIN) AF: 0.000375 AC: 20 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4376

European-Non Finnish (NFE) AF: 0.00130 AC: 1441 AN: 1111444

Other (OTH) AF: 0.000532 AC: 32 AN: 60204

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.000377 AC XY: 28 AN XY: 74342

African (AFR) AF: 0.000410 AC: 17 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000823 AC: 56 AN: 68024

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000638 Hom.: 0

Bravo AF: 0.000457

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.3
DANN	Benign	0.28
PhyloP100		0.85
Mutation Taster		=98/2	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: rs201092091; hg19: chr18-3116341;