10-93478104-C-T

Variant names:

• chr10-93478104-C-T
• rs2096181
• NM_013451.4:c.88+4003G>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+4003G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 229,168 control chromosomes in the GnomAD database, including 74,098 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 (46299 hom., cov: 31)
  • Exomes 𝑓: 0.85 (27799 hom.)
• Consequence: MYOF NM_013451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• 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=-0.99).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOF	NM_013451.4	MANE Select	c.88+4003G>A		intron	N/A	NP_038479.1
	MYOF	NM_133337.3		c.88+4003G>A		intron	N/A	NP_579899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOF	ENST00000359263.9	TSL:1 MANE Select	c.88+4003G>A		intron	N/A	ENSP00000352208.4
	MYOF	ENST00000358334.9	TSL:1	c.88+4003G>A		intron	N/A	ENSP00000351094.5
	MYOF	ENST00000371489.5	TSL:2	c.88+4003G>A		intron	N/A	ENSP00000360544.1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 117938 AN: 151834 Hom.: 46262 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.777

GnomAD4 exome AF: 0.846 AC: 65295 AN: 77216 Hom.: 27799 AF XY: 0.842 AC XY: 42191 AN XY: 50102

African (AFR) AF: 0.763 AC: 746 AN: 978

American (AMR) AF: 0.842 AC: 2590 AN: 3076

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 1761 AN: 2230

East Asian (EAS) AF: 0.605 AC: 1402 AN: 2318

South Asian (SAS) AF: 0.875 AC: 10510 AN: 12012

European-Finnish (FIN) AF: 0.823 AC: 2275 AN: 2764

Middle Eastern (MID) AF: 0.748 AC: 184 AN: 246

European-Non Finnish (NFE) AF: 0.857 AC: 42932 AN: 50080

Other (OTH) AF: 0.824 AC: 2895 AN: 3512

GnomAD4 genome AF: 0.777 AC: 118030 AN: 151952 Hom.: 46299 Cov.: 31 AF XY: 0.773 AC XY: 57374 AN XY: 74246

African (AFR) AF: 0.700 AC: 29009 AN: 41426

American (AMR) AF: 0.789 AC: 12042 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2704 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2475 AN: 5158

South Asian (SAS) AF: 0.843 AC: 4061 AN: 4816

European-Finnish (FIN) AF: 0.765 AC: 8023 AN: 10488

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

European-Non Finnish (NFE) AF: 0.839 AC: 57090 AN: 68006

Other (OTH) AF: 0.777 AC: 1644 AN: 2116

Alfa AF: 0.799 Hom.: 7375

Bravo AF: 0.769

Asia WGS AF: 0.675 AC: 2342 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.1
DANN	Benign	0.16
PhyloP100		0.16
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: rs2096181; hg19: chr10-95237861;