10-93474725-T-C

Variant names:

• chr10-93474725-T-C
• rs2004558
• NM_013451.4:c.88+7382A>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.88+7382A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 151,706 control chromosomes in the GnomAD database, including 46,276 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 0.78 (46276 hom., cov: 30)
• Consequence: MYOF NM_013451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.834 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.88+7382A>G		intron	N/A	NP_038479.1	Q9NZM1-1
	MYOF	NM_133337.3		c.88+7382A>G		intron	N/A	NP_579899.1	Q9NZM1-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOF	ENST00000359263.9	TSL:1 MANE Select	c.88+7382A>G		intron	N/A	ENSP00000352208.4	Q9NZM1-1
	MYOF	ENST00000358334.9	TSL:1	c.88+7382A>G		intron	N/A	ENSP00000351094.5	Q9NZM1-6
	MYOF	ENST00000941957.1		c.88+7382A>G		intron	N/A	ENSP00000612016.1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 117825 AN: 151592 Hom.: 46240 Cov.: 30

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.777 AC: 117914 AN: 151706 Hom.: 46276 Cov.: 30 AF XY: 0.773 AC XY: 57264 AN XY: 74060

African (AFR) AF: 0.701 AC: 29016 AN: 41388

American (AMR) AF: 0.789 AC: 12008 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2703 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2495 AN: 5148

South Asian (SAS) AF: 0.848 AC: 4080 AN: 4814

European-Finnish (FIN) AF: 0.763 AC: 7930 AN: 10394

Middle Eastern (MID) AF: 0.784 AC: 229 AN: 292

European-Non Finnish (NFE) AF: 0.840 AC: 57064 AN: 67954

Other (OTH) AF: 0.776 AC: 1636 AN: 2108

Alfa AF: 0.800 Hom.: 8191

Bravo AF: 0.770

Asia WGS AF: 0.673 AC: 2339 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	2.6
DANN	Benign	0.69
PhyloP100		0.23
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: rs2004558; hg19: chr10-95234482;