chr12-80707939-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002469.3(MYF6):c.220C>T(p.Pro74Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000743 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
MYF6
NM_002469.3 missense
NM_002469.3 missense
Scores
2
12
5
Clinical Significance
Conservation
PhyloP100: 4.08
Genes affected
MYF6 (HGNC:7566): (myogenic factor 6) The protein encoded by this gene is a probable basic helix-loop-helix (bHLH) DNA binding protein involved in muscle differentiation. The encoded protein likely acts as a heterodimer with another bHLH protein. Defects in this gene are a cause of autosomal dominant centronuclear myopathy (ADCNM). [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYF6 | NM_002469.3 | c.220C>T | p.Pro74Ser | missense_variant | 1/3 | ENST00000228641.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYF6 | ENST00000228641.4 | c.220C>T | p.Pro74Ser | missense_variant | 1/3 | 1 | NM_002469.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152144Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250728Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135730
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727238
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74326
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 18, 2023 | The c.220C>T (p.P74S) alteration is located in exon 1 (coding exon 1) of the MYF6 gene. This alteration results from a C to T substitution at nucleotide position 220, causing the proline (P) at amino acid position 74 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autosomal dominant centronuclear myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 29, 2019 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MYF6-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 74 of the MYF6 protein (p.Pro74Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of catalytic residue at L78 (P = 0);
MVP
MPC
ClinPred
D
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