Genetic Variant MYOF:c.5999+6_5999+7delAG (chr10-93310526-CCT-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

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

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.24

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOF	NM_013451.4 link	c.5999+6_5999+7delAG		splice_region_variant, intron_variant	Intron 52 of 53	ENST00000359263.9	NP_038479.1	Q9NZM1-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYOF	ENST00000359263.9 link	c.5999+6_5999+7delAG	splice_region_variant, intron_variant	Intron 52 of 53	1	NM_013451.4	ENSP00000352208.4	Q9NZM1-1
MYOF	ENST00000358334.9 link	c.5960+6_5960+7delAG	splice_region_variant, intron_variant	Intron 51 of 52	1		ENSP00000351094.5	Q9NZM1-6
MYOF	ENST00000463743.5 link	n.558+6_558+7delAG	splice_region_variant, intron_variant	Intron 32 of 33	5		ENSP00000432708.1	H0YD14

Frequencies

GnomAD3 genomes

AF:

0.0349

AC:

5302

AN:

152112

Hom.:

301

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00894

AC:

2227

AN:

249216

Hom.:

138

AF XY:

0.00679

AC XY:

918

AN XY:

135206

show subpopulations

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 SAS exome

AF:

0.000229

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

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.00682

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.000229

Gnomad4 OTH exome

AF:

0.00866

GnomAD4 genome

AF:

0.0350

AC:

5325

AN:

152230

Hom.:

304

Cov.:

AF XY:

0.0343

AC XY:

2550

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.00974

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0303

Alfa

AF:

0.0190

Hom.:

Bravo

AF:

0.0398

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MYOF-related disorder

Benign:1

Jul 03, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over