rs369620858

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_013451.4(MYOF):c.5879G>A(p.Arg1960His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,608,930 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1960C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 3 hom. )

Consequence

MYOF
NM_013451.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

angioedema, hereditary, 7
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MYOF links:

ENSG00000297060 (HGNC:):

ENSG00000297060 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 3 Unknown gene

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.5879G>A	p.Arg1960His	missense	Exon 51 of 54	NP_038479.1	Q9NZM1-1
	MYOF	NM_133337.3		c.5840G>A	p.Arg1947His	missense	Exon 50 of 53	NP_579899.1	Q9NZM1-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYOF	ENST00000359263.9	TSL:1 MANE Select	c.5879G>A	p.Arg1960His	missense	Exon 51 of 54	ENSP00000352208.4	Q9NZM1-1
MYOF	ENST00000358334.9	TSL:1	c.5840G>A	p.Arg1947His	missense	Exon 50 of 53	ENSP00000351094.5	Q9NZM1-6
MYOF	ENST00000941957.1		c.6008G>A	p.Arg2003His	missense	Exon 52 of 55	ENSP00000612016.1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000106

AC:

AN:

245212

AF XY:

0.000105

show subpopulations

Gnomad AFR exome

AF:

0.000389

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000168

Gnomad FIN exome

AF:

0.0000931

Gnomad NFE exome

AF:

0.0000984

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000106

AC:

154

AN:

1456740

Hom.:

Cov.:

AF XY:

0.0000952

AC XY:

AN XY:

724454

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

33236

American (AMR)

AF:

0.0000683

AC:

AN:

43920

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

25962

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39608

South Asian (SAS)

AF:

0.0000705

AC:

AN:

85072

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00495

AC:

AN:

5248

European-Non Finnish (NFE)

AF:

0.0000856

AC:

AN:

1110154

Other (OTH)

AF:

0.000166

AC:

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000210

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.000459

AC:

AN:

41434

American (AMR)

AF:

0.000393

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.000524

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000179

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.11

Eigen_PC

Benign

0.023

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.022

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.41

MutationAssessor

Benign

1.2

PhyloP100

1.8

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.30

Sift

Uncertain

0.0080

Sift4G

Benign

0.57

Polyphen

0.043

Vest4

0.18

MVP

0.84

MPC

0.19

ClinPred

0.071

GERP RS

5.3

Varity_R

0.19

gMVP

0.63

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.44

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.44

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over