rs787634

Variant names:

• chr10-93360162-T-C
• rs787634
• NM_013451.4:c.2975-184A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013451.4(MYOF):​c.2975-184A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,194 control chromosomes in the GnomAD database, including 7,923 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 0.30 (7923 hom., cov: 33)
• Consequence: MYOF NM_013451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 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.2975-184A>G		intron	N/A	NP_038479.1	Q9NZM1-1
	MYOF	NM_133337.3		c.2936-184A>G		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.2975-184A>G		intron	N/A	ENSP00000352208.4	Q9NZM1-1
	MYOF	ENST00000358334.9	TSL:1	c.2936-184A>G		intron	N/A	ENSP00000351094.5	Q9NZM1-6
	MYOF	ENST00000941957.1		c.2975-184A>G		intron	N/A	ENSP00000612016.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45816 AN: 152076 Hom.: 7920 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.0961

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.303

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.301 AC: 45835 AN: 152194 Hom.: 7923 Cov.: 33 AF XY: 0.297 AC XY: 22125 AN XY: 74410

African (AFR) AF: 0.148 AC: 6166 AN: 41538

American (AMR) AF: 0.242 AC: 3706 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3470

East Asian (EAS) AF: 0.0963 AC: 500 AN: 5190

South Asian (SAS) AF: 0.287 AC: 1385 AN: 4826

European-Finnish (FIN) AF: 0.442 AC: 4673 AN: 10564

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27189 AN: 67998

Other (OTH) AF: 0.306 AC: 647 AN: 2116

Alfa AF: 0.313 Hom.: 2598

Bravo AF: 0.280

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.40
PhyloP100		0.18
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: rs787634; hg19: chr10-95119919; COSMIC: COSV107452763;