NM_013451.4:c.6000-113T>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013451.4(MYOF):​c.6000-113T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1200224 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 594392

African (AFR) AF: 0.00 AC: 0 AN: 27394

American (AMR) AF: 0.00 AC: 0 AN: 31036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19820

East Asian (EAS) AF: 0.00 AC: 0 AN: 37902

South Asian (SAS) AF: 0.00 AC: 0 AN: 66790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5072

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 913472

Other (OTH) AF: 0.00 AC: 0 AN: 51006

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 69766

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.37
PhyloP100		-0.26

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: rs2761286; hg19: chr10-95070037;