NM_013451.4:c.5999+6_5999+7delAG

Variant names:

• chr10-93310526-CCT-C
• rs147504979
• NM_013451.4:c.5999+6_5999+7delAG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_013451.4(MYOF):​c.5999+6_5999+7delAG variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00668 in 1,613,412 control chromosomes in the GnomAD database, including 616 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.035 (304 hom., cov: 31)
  • Exomes 𝑓: 0.0037 (312 hom.)
• Consequence: MYOF NM_013451.4 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.24
• 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)

ENSG00000297060 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 10-93310526-CCT-C is Benign according to our data. Variant chr10-93310526-CCT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3345588.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOF	NM_013451.4	MANE Select	c.5999+6_5999+7delAG		splice_region intron	N/A	NP_038479.1	Q9NZM1-1
	MYOF	NM_133337.3		c.5960+6_5960+7delAG		splice_region intron	N/A	NP_579899.1	Q9NZM1-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOF	ENST00000359263.9	TSL:1 MANE Select	c.5999+6_5999+7delAG		splice_region intron	N/A	ENSP00000352208.4	Q9NZM1-1
	MYOF	ENST00000358334.9	TSL:1	c.5960+6_5960+7delAG		splice_region intron	N/A	ENSP00000351094.5	Q9NZM1-6
	MYOF	ENST00000941957.1		c.6128+6_6128+7delAG		splice_region intron	N/A	ENSP00000612016.1

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5302 AN: 152112 Hom.: 301 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0307

GnomAD2 exomes AF: 0.00894 AC: 2227 AN: 249216 AF XY: 0.00679

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.00604

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.000416

Gnomad OTH exome AF: 0.00397

GnomAD4 exome AF: 0.00373 AC: 5451 AN: 1461182 Hom.: 312 AF XY: 0.00321 AC XY: 2333 AN XY: 726932

African (AFR) AF: 0.128 AC: 4274 AN: 33444

American (AMR) AF: 0.00682 AC: 305 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86218

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53416

Middle Eastern (MID) AF: 0.0101 AC: 58 AN: 5768

European-Non Finnish (NFE) AF: 0.000229 AC: 254 AN: 1111460

Other (OTH) AF: 0.00866 AC: 523 AN: 60370

GnomAD4 genome AF: 0.0350 AC: 5325 AN: 152230 Hom.: 304 Cov.: 31 AF XY: 0.0343 AC XY: 2550 AN XY: 74438

African (AFR) AF: 0.122 AC: 5082 AN: 41528

American (AMR) AF: 0.00974 AC: 149 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68012

Other (OTH) AF: 0.0303 AC: 64 AN: 2110

Alfa AF: 0.0190 Hom.: 31

Bravo AF: 0.0398

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MYOF-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2
Mutation Taster		=81/19	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: rs147504979; hg19: chr10-95070283;