NM_003970.4:c.4081-104C>T

Variant names:

• chr8-2144560-C-T
• rs10503170
• NM_003970.4:c.4081-104C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003970.4(MYOM2):​c.4081-104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,141,538 control chromosomes in the GnomAD database, including 26,636 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 0.17 (2761 hom., cov: 33)
  • Exomes 𝑓: 0.21 (23875 hom.)
• Consequence: MYOM2 NM_003970.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• Publications: 5 publications found

Genes affected

MYOM2 (HGNC:7614): (myomesin 2) 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 and 165 kD. The predicted MYOM2 protein contains 1,465 amino acids. Like MYOM1, MYOM2 has a unique N-terminal domain followed by 12 repeat domains with strong homology to either fibronectin type III or immunoglobulin C2 domains. Protein sequence comparisons suggested that the MYOM2 protein and bovine M protein are identical. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003970.4. 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
	MYOM2	NM_003970.4	MANE Select	c.4081-104C>T		intron	N/A	NP_003961.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM2	ENST00000262113.9	TSL:1 MANE Select	c.4081-104C>T		intron	N/A	ENSP00000262113.4
	MYOM2	ENST00000887732.1		c.4174-104C>T		intron	N/A	ENSP00000557791.1
	MYOM2	ENST00000887733.1		c.4162-104C>T		intron	N/A	ENSP00000557792.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26474 AN: 152032 Hom.: 2764 Cov.: 33

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.215 AC: 212345 AN: 989388 Hom.: 23875 AF XY: 0.214 AC XY: 109299 AN XY: 509952

African (AFR) AF: 0.0552 AC: 1240 AN: 22444

American (AMR) AF: 0.129 AC: 3982 AN: 30934

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 4538 AN: 21466

East Asian (EAS) AF: 0.199 AC: 7455 AN: 37458

South Asian (SAS) AF: 0.198 AC: 14157 AN: 71404

European-Finnish (FIN) AF: 0.233 AC: 11880 AN: 50950

Middle Eastern (MID) AF: 0.241 AC: 1160 AN: 4822

European-Non Finnish (NFE) AF: 0.225 AC: 158463 AN: 705390

Other (OTH) AF: 0.213 AC: 9470 AN: 44520

GnomAD4 genome AF: 0.174 AC: 26468 AN: 152150 Hom.: 2761 Cov.: 33 AF XY: 0.176 AC XY: 13122 AN XY: 74388

African (AFR) AF: 0.0583 AC: 2422 AN: 41534

American (AMR) AF: 0.186 AC: 2837 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 755 AN: 3472

East Asian (EAS) AF: 0.182 AC: 938 AN: 5150

South Asian (SAS) AF: 0.191 AC: 919 AN: 4822

European-Finnish (FIN) AF: 0.249 AC: 2636 AN: 10592

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15273 AN: 67972

Other (OTH) AF: 0.221 AC: 467 AN: 2112

Alfa AF: 0.190 Hom.: 1701

Bravo AF: 0.167

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.62
PhyloP100		0.14
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: rs10503170; hg19: chr8-2092484; COSMIC: COSV107255675; COSMIC: COSV107255675;