10-93443647-T-C

Variant names:

• chr10-93443647-T-C
• rs766083
• NM_013451.4:c.236+8403A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

MYOF Gene-Disease associations (from GenCC):

• angioedema, hereditary, 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013451.4. 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
	MYOF	NM_013451.4	MANE Select	c.236+8403A>G		intron	N/A	NP_038479.1
	MYOF	NM_133337.3		c.236+8403A>G		intron	N/A	NP_579899.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOF	ENST00000359263.9	TSL:1 MANE Select	c.236+8403A>G		intron	N/A	ENSP00000352208.4
	MYOF	ENST00000358334.9	TSL:1	c.236+8403A>G		intron	N/A	ENSP00000351094.5
	MYOF	ENST00000941957.1		c.236+8403A>G		intron	N/A	ENSP00000612016.1

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

African (AFR) AF: 0.413 AC: 17110 AN: 41382

American (AMR) AF: 0.646 AC: 9862 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1919 AN: 3464

East Asian (EAS) AF: 0.767 AC: 3966 AN: 5168

South Asian (SAS) AF: 0.643 AC: 3091 AN: 4810

European-Finnish (FIN) AF: 0.824 AC: 8706 AN: 10564

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47198 AN: 67968

Other (OTH) AF: 0.589 AC: 1241 AN: 2108

Alfa AF: 0.624 Hom.: 5906

Bravo AF: 0.599

Asia WGS AF: 0.661 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.060
DANN	Benign	0.62
PhyloP100		-2.7
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: rs766083; hg19: chr10-95203404;