rs6890689
Positions:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_006790.3(MYOT):c.220C>A(p.Gln74Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00253 in 1,614,194 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.013 ( 44 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 44 hom. )
Consequence
MYOT
NM_006790.3 missense
NM_006790.3 missense
Scores
5
Clinical Significance
Conservation
PhyloP100: 3.80
Genes affected
MYOT (HGNC:12399): (myotilin) This gene encodes a cystoskeletal protein which plays a significant role in the stability of thin filaments during muscle contraction. This protein binds F-actin, crosslinks actin filaments, and prevents latrunculin A-induced filament disassembly. Mutations in this gene have been associated with limb-girdle muscular dystrophy and myofibrillar myopathies. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.[provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.07220766).
BP6
?
Variant 5-137870871-C-A is Benign according to our data. Variant chr5-137870871-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 464369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2048/152308) while in subpopulation AFR AF= 0.0463 (1926/41554). AF 95% confidence interval is 0.0446. There are 44 homozygotes in gnomad4. There are 965 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 2048 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOT | NM_006790.3 | c.220C>A | p.Gln74Lys | missense_variant | 2/10 | ENST00000239926.9 | |
PKD2L2-DT | XR_948815.3 | n.303-11608G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOT | ENST00000239926.9 | c.220C>A | p.Gln74Lys | missense_variant | 2/10 | 1 | NM_006790.3 | P1 | |
PKD2L2-DT | ENST00000514616.6 | n.320-11608G>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0134 AC: 2040AN: 152190Hom.: 44 Cov.: 32
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GnomAD4 exome AF: 0.00140 AC: 2040AN: 1461886Hom.: 44 Cov.: 31 AF XY: 0.00121 AC XY: 877AN XY: 727246
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GnomAD4 genome ? AF: 0.0134 AC: 2048AN: 152308Hom.: 44 Cov.: 32 AF XY: 0.0130 AC XY: 965AN XY: 74488
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 09, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 28, 2017 | - - |
Myofibrillar myopathy 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_noAF
Benign
CADD
Benign
LIST_S2
Benign
T
MetaRNN
Benign
T
Sift4G
Benign
T
Vest4
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at