NM_013451.4:c.88+1005C>A

Variant names:

• chr10-93481102-G-T
• rs7900392
• NM_013451.4:c.88+1005C>A

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+1005C>A 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 152,108 control chromosomes in the GnomAD database, including 46,337 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 (46337 hom., cov: 32)
• Consequence: MYOF NM_013451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOF	NM_013451.4	c.88+1005C>A		intron_variant	Intron 1 of 53	ENST00000359263.9	NP_038479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOF	ENST00000359263.9	c.88+1005C>A		intron_variant	Intron 1 of 53	1	NM_013451.4	ENSP00000352208.4

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118047 AN: 151990 Hom.: 46297 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.777 AC: 118143 AN: 152108 Hom.: 46337 Cov.: 32 AF XY: 0.773 AC XY: 57452 AN XY: 74348

African (AFR) AF: 0.701 AC: 29039 AN: 41450

American (AMR) AF: 0.788 AC: 12046 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2704 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2479 AN: 5162

South Asian (SAS) AF: 0.844 AC: 4074 AN: 4828

European-Finnish (FIN) AF: 0.764 AC: 8089 AN: 10592

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57087 AN: 67996

Other (OTH) AF: 0.776 AC: 1641 AN: 2116

Alfa AF: 0.801 Hom.: 6025

Bravo AF: 0.769

Asia WGS AF: 0.674 AC: 2345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.40
PhyloP100		0.49
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: rs7900392; hg19: chr10-95240859;