rs6506070

Variant names:

• chr18-3141691-G-A
• rs6506070
• NM_003803.4:c.2025+248C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003803.4(MYOM1):​c.2025+248C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,046 control chromosomes in the GnomAD database, including 24,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (24088 hom., cov: 31)
• Consequence: MYOM1 NM_003803.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.267
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-3141691-G-A is Benign according to our data. Variant chr18-3141691-G-A is described in ClinVar as Benign. ClinVar VariationId is 1222056.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM1	NM_003803.4	c.2025+248C>T		intron_variant	Intron 14 of 37	ENST00000356443.9	NP_003794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOM1	ENST00000356443.9	c.2025+248C>T		intron_variant	Intron 14 of 37	1	NM_003803.4	ENSP00000348821.4
MYOM1	ENST00000261606.11	c.2025+248C>T		intron_variant	Intron 14 of 36	1		ENSP00000261606.7
MYOM1	ENST00000577294.1	n.81+248C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 83014 AN: 151928 Hom.: 24039 Cov.: 31

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.547 AC: 83126 AN: 152046 Hom.: 24088 Cov.: 31 AF XY: 0.536 AC XY: 39877 AN XY: 74346

African (AFR) AF: 0.738 AC: 30605 AN: 41460

American (AMR) AF: 0.576 AC: 8803 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1642 AN: 3466

East Asian (EAS) AF: 0.283 AC: 1468 AN: 5182

South Asian (SAS) AF: 0.478 AC: 2303 AN: 4822

European-Finnish (FIN) AF: 0.363 AC: 3840 AN: 10568

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32852 AN: 67956

Other (OTH) AF: 0.542 AC: 1145 AN: 2112

Alfa AF: 0.503 Hom.: 84591

Bravo AF: 0.569

Asia WGS AF: 0.400 AC: 1391 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.21
PhyloP100		-0.27
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: rs6506070; hg19: chr18-3141689;