10-93310598-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_013451.4(MYOF):c.5935G>A(p.Asp1979Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,614,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
MYOF
NM_013451.4 missense
NM_013451.4 missense
Scores
2
8
7
Clinical Significance
Conservation
PhyloP100: 6.17
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.06365627).
BS2
High AC in GnomAd4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOF | NM_013451.4 | c.5935G>A | p.Asp1979Asn | missense_variant | 52/54 | ENST00000359263.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOF | ENST00000359263.9 | c.5935G>A | p.Asp1979Asn | missense_variant | 52/54 | 1 | NM_013451.4 | P1 | |
MYOF | ENST00000358334.9 | c.5896G>A | p.Asp1966Asn | missense_variant | 51/53 | 1 | |||
MYOF | ENST00000463743.5 | c.*494G>A | 3_prime_UTR_variant, NMD_transcript_variant | 32/34 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000120 AC: 30AN: 249554Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135388
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 727236
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GnomAD4 genome AF: 0.0000919 AC: 14AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74476
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 13, 2023 | The c.5935G>A (p.D1979N) alteration is located in exon 52 (coding exon 52) of the MYOF gene. This alteration results from a G to A substitution at nucleotide position 5935, causing the aspartic acid (D) at amino acid position 1979 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MVP
MPC
0.35
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at