rs766083

chr10-93443647-T-Cchr10-93443647-T-G

Variant summary

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

The NM_013451.4(MYOF):c.236+8403A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,940 control chromosomes in the GnomAD database, including 30,470 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 0.62 (30470 hom., cov: 30)
• Consequence: MYOF NM_013451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOF	NM_013451.4	c.236+8403A>G		intron_variant		ENST00000359263.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOF	ENST00000359263.9	c.236+8403A>G		intron_variant		1	NM_013451.4	P1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 93924 AN: 151822 Hom.: 30460 Cov.: 30

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.618 AC: 93961 AN: 151940 Hom.: 30470 Cov.: 30 AF XY: 0.624 AC XY: 46316 AN XY: 74228

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.589

Alfa AF: 0.629 Hom.: 5837

Bravo AF: 0.599

Asia WGS AF: 0.661 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.060
Dann	Benign	0.62

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: rs766083; hg19: chr10-95203404;