rs4798069

chr18-3163773-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003803.4(MYOM1):c.1501+505G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,816 control chromosomes in the GnomAD database, including 10,679 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 0.37 (10679 hom., cov: 32)
• Consequence: MYOM1 NM_003803.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOM1	NM_003803.4	c.1501+505G>A		intron_variant		ENST00000356443.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOM1	ENST00000356443.9	c.1501+505G>A		intron_variant		1	NM_003803.4	P2
MYOM1	ENST00000261606.11	c.1501+505G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55986 AN: 151698 Hom.: 10670 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.369 AC: 56031 AN: 151816 Hom.: 10679 Cov.: 32 AF XY: 0.375 AC XY: 27789 AN XY: 74186

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.360

Alfa AF: 0.311 Hom.: 10165

Bravo AF: 0.369

Asia WGS AF: 0.417 AC: 1449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.0
Dann	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs4798069; hg19: chr18-3163771;