chr10-93313142-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_013451.4(MYOF):c.5767A>T(p.Met1923Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
MYOF
NM_013451.4 missense
NM_013451.4 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 4.02
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOF | NM_013451.4 | c.5767A>T | p.Met1923Leu | missense_variant | 51/54 | ENST00000359263.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOF | ENST00000359263.9 | c.5767A>T | p.Met1923Leu | missense_variant | 51/54 | 1 | NM_013451.4 | P1 | |
MYOF | ENST00000358334.9 | c.5728A>T | p.Met1910Leu | missense_variant | 50/53 | 1 | |||
MYOF | ENST00000463743.5 | c.*326A>T | 3_prime_UTR_variant, NMD_transcript_variant | 31/34 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249458Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135336
GnomAD3 exomes
AF:
AC:
1
AN:
249458
Hom.:
AF XY:
AC XY:
1
AN XY:
135336
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461828Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 727212
GnomAD4 exome
AF:
AC:
1
AN:
1461828
Hom.:
Cov.:
29
AF XY:
AC XY:
1
AN XY:
727212
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Alfa
AF:
Hom.:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | MYOF: PM2, BP4 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
0.42
.;Loss of methylation at K1928 (P = 0.0746);
MVP
MPC
0.14
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at