rs10153321

chr18-3176379-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003803.4(MYOM1):c.930-245C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0865 in 152,160 control chromosomes in the GnomAD database, including 726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.086 (726 hom., cov: 32)
• Consequence: MYOM1 NM_003803.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.252

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 18-3176379-G-A is Benign according to our data. Variant chr18-3176379-G-A is described in ClinVar as [Benign]. Clinvar id is 1251258.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOM1	NM_003803.4	c.930-245C>T		intron_variant		ENST00000356443.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOM1	ENST00000356443.9	c.930-245C>T		intron_variant		1	NM_003803.4	P2
MYOM1	ENST00000261606.11	c.930-245C>T		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.0865 AC: 13156 AN: 152042 Hom.: 724 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0749

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.0841

Gnomad FIN AF: 0.0725

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0958

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

GnomAD4 genome AF: 0.0865 AC: 13161 AN: 152160 Hom.: 726 Cov.: 32 AF XY: 0.0875 AC XY: 6512 AN XY: 74388

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.0864

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.0837

Gnomad4 FIN AF: 0.0725

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.0948

Alfa AF: 0.0652 Hom.: 477

Bravo AF: 0.0891

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.6
Dann	Benign	0.39

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: rs10153321; hg19: chr18-3176377;