rs138208183

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013451.4(MYOF):c.5719C>T(p.Arg1907Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000157 in 1,613,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

MYOF
NM_013451.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 5.71

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.041573286).

BS2

High AC in GnomAd4 at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOF	NM_013451.4 link	c.5719C>T	p.Arg1907Cys	missense_variant	Exon 51 of 54	ENST00000359263.9	NP_038479.1	Q9NZM1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYOF	ENST00000359263.9 link	c.5719C>T	p.Arg1907Cys	missense_variant	Exon 51 of 54	1	NM_013451.4	ENSP00000352208.4	Q9NZM1-1
MYOF	ENST00000358334.9 link	c.5680C>T	p.Arg1894Cys	missense_variant	Exon 50 of 53	1		ENSP00000351094.5	Q9NZM1-6
MYOF	ENST00000463743.5 link	n.*278C>T		non_coding_transcript_exon_variant	Exon 31 of 34	5		ENSP00000432708.1	H0YD14
MYOF	ENST00000463743.5 link	n.*278C>T		3_prime_UTR_variant	Exon 31 of 34	5		ENSP00000432708.1	H0YD14

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000176

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000165

AC:

AN:

248182

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

134638

show subpopulations

Gnomad AFR exome

AF:

0.00116

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000128

AC:

187

AN:

1460956

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

726742

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000440

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000555

ESP6500AA

AF:

0.000758

AC:

ESP6500EA

AF:

0.000360

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5719C>T (p.R1907C) alteration is located in exon 51 (coding exon 51) of the MYOF gene. This alteration results from a C to T substitution at nucleotide position 5719, causing the arginine (R) at amino acid position 1907 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

MYOF-related disorder

Uncertain:1

Jul 03, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The MYOF c.5719C>T variant is predicted to result in the amino acid substitution p.Arg1907Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.11% of alleles in individuals of African descent in gnomAD, which may be too common to be causative. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

0.10

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.0

.;L

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.19

Sift

Benign

0.043

D;D

Sift4G

Benign

0.24

T;T

Polyphen

0.72

P;B

Vest4

0.35

MVP

0.89

MPC

0.41

ClinPred

0.070

GERP RS

5.4

Varity_R

0.16

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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