rs787625

Positions:

• chr10-93353734-A-G

Variant summary

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

The NM_013451.4(MYOF):​c.3481+77T>C variant causes a intron change. The variant allele was found at a frequency of 0.375 in 1,200,024 control chromosomes in the GnomAD database, including 89,565 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 0.33 (8776 hom., cov: 32)
  • Exomes 𝑓: 0.38 (80789 hom.)
• Consequence: MYOF NM_013451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09

Genes affected

MYOF (HGNC:3656): (myoferlin) Mutations in dysferlin, a protein associated with the plasma membrane, can cause muscle weakness that affects both proximal and distal muscles. The protein encoded by this gene is a type II membrane protein that is structurally similar to dysferlin. It is a member of the ferlin family and associates with both plasma and nuclear membranes. The protein contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. Two transcript variants encoding different isoforms have been found for this gene. Other possible variants have been detected, but their full-length nature has not been determined. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOF	NM_013451.4	c.3481+77T>C		intron_variant		ENST00000359263.9	NP_038479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOF	ENST00000359263.9	c.3481+77T>C		intron_variant		1	NM_013451.4	ENSP00000352208.4
MYOF	ENST00000358334.9	c.3442+77T>C		intron_variant		1		ENSP00000351094.5
MYOF	ENST00000463743.5	n.1603+77T>C		intron_variant		5		ENSP00000432708.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49408 AN: 151960 Hom.: 8771 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.0915

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.382 AC: 400312 AN: 1047946 Hom.: 80789 AF XY: 0.381 AC XY: 200933 AN XY: 527596

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.366

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.325 AC: 49435 AN: 152078 Hom.: 8776 Cov.: 32 AF XY: 0.320 AC XY: 23803 AN XY: 74314

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.0917

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.335

Alfa AF: 0.370 Hom.: 2151

Bravo AF: 0.307

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.8
DANN	Benign	0.79

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: rs787625; hg19: chr10-95113491; COSMIC: COSV63703860;