18-3138555-A-G

Variant names:

• chr18-3138555-A-G
• rs4797100
• NM_003803.4:c.2026-2825T>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.2026-2825T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,022 control chromosomes in the GnomAD database, including 5,167 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 0.25 (5167 hom., cov: 32)
• Consequence: MYOM1 NM_003803.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• 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 (EAS) allele frequency at 95% confidence interval = 0.41 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.2026-2825T>C		intron	N/A	NP_003794.3
	MYOM1	NM_019856.2		c.2026-2825T>C		intron	N/A	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.2026-2825T>C		intron	N/A	ENSP00000348821.4	P52179-1
	MYOM1	ENST00000261606.11	TSL:1	c.2026-2825T>C		intron	N/A	ENSP00000261606.7	P52179-2
	MYOM1	ENST00000941943.1		c.2026-2825T>C		intron	N/A	ENSP00000612002.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38392 AN: 151904 Hom.: 5164 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.253 AC: 38405 AN: 152022 Hom.: 5167 Cov.: 32 AF XY: 0.257 AC XY: 19069 AN XY: 74318

African (AFR) AF: 0.231 AC: 9598 AN: 41472

American (AMR) AF: 0.187 AC: 2863 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3468

East Asian (EAS) AF: 0.425 AC: 2193 AN: 5164

South Asian (SAS) AF: 0.252 AC: 1216 AN: 4824

European-Finnish (FIN) AF: 0.359 AC: 3789 AN: 10552

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17258 AN: 67942

Other (OTH) AF: 0.221 AC: 468 AN: 2114

Alfa AF: 0.243 Hom.: 14950

Bravo AF: 0.238

Asia WGS AF: 0.355 AC: 1233 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	1.8
DANN	Benign	0.27
PhyloP100		-0.17
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: rs4797100; hg19: chr18-3138553;