10-93310280-A-G

Position:

• chr10-93310280-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	Protein	UniProt
MYOF	NM_013451.4	c.6000-113T>C		intron_variant		ENST00000359263.9	NP_038479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOF	ENST00000359263.9	c.6000-113T>C		intron_variant		1	NM_013451.4	ENSP00000352208.4
MYOF	ENST00000358334.9	c.5961-113T>C		intron_variant		1		ENSP00000351094.5
MYOF	ENST00000463743.5	n.*559-113T>C		intron_variant		5		ENSP00000432708.1

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

Gnomad4 AFR exome AF: 0.844

Gnomad4 AMR exome AF: 0.785

Gnomad4 ASJ exome AF: 0.808

Gnomad4 EAS exome AF: 0.896

Gnomad4 SAS exome AF: 0.864

Gnomad4 FIN exome AF: 0.879

Gnomad4 NFE exome AF: 0.848

Gnomad4 OTH exome AF: 0.845

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

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.819

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.842

Alfa AF: 0.851 Hom.: 52962

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2761286; hg19: chr10-95070037;