10-93310280-A-G

Variant names:

• chr10-93310280-A-G
• rs2761286
• NM_013451.4:c.6000-113T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013451.4(MYOF):​c.6000-113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 1,350,956 control chromosomes in the GnomAD database, including 487,909 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 0.85 (55124 hom., cov: 32)
  • Exomes 𝑓: 0.85 (432785 hom.)
• Consequence: MYOF NM_013451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 4 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)

ENSG00000297060 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOF	NM_013451.4	c.6000-113T>C		intron_variant	Intron 52 of 53	ENST00000359263.9	NP_038479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOF	ENST00000359263.9	c.6000-113T>C		intron_variant	Intron 52 of 53	1	NM_013451.4	ENSP00000352208.4

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129350 AN: 152064 Hom.: 55091 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.847

GnomAD4 exome AF: 0.849 AC: 1018191 AN: 1198774 Hom.: 432785 AF XY: 0.850 AC XY: 504785 AN XY: 593708

African (AFR) AF: 0.844 AC: 23089 AN: 27362

American (AMR) AF: 0.785 AC: 24329 AN: 30996

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 15992 AN: 19798

East Asian (EAS) AF: 0.896 AC: 33963 AN: 37898

South Asian (SAS) AF: 0.864 AC: 57648 AN: 66750

European-Finnish (FIN) AF: 0.879 AC: 41929 AN: 47698

Middle Eastern (MID) AF: 0.853 AC: 4324 AN: 5070

European-Non Finnish (NFE) AF: 0.848 AC: 773854 AN: 912240

Other (OTH) AF: 0.845 AC: 43063 AN: 50962

GnomAD4 genome AF: 0.851 AC: 129437 AN: 152182 Hom.: 55124 Cov.: 32 AF XY: 0.853 AC XY: 63454 AN XY: 74412

African (AFR) AF: 0.847 AC: 35164 AN: 41498

American (AMR) AF: 0.819 AC: 12531 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2758 AN: 3470

East Asian (EAS) AF: 0.905 AC: 4682 AN: 5176

South Asian (SAS) AF: 0.870 AC: 4198 AN: 4824

European-Finnish (FIN) AF: 0.875 AC: 9279 AN: 10604

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58164 AN: 68004

Other (OTH) AF: 0.842 AC: 1777 AN: 2110

Alfa AF: 0.850 Hom.: 69766

Bravo AF: 0.843

Asia WGS AF: 0.834 AC: 2898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.9
DANN	Benign	0.23
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2761286; hg19: chr10-95070037;