NM_001927.4:c.1353C>T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_001927.4(DES):c.1353C>T(p.Ile451Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,602,978 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001927.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000250 AC: 38AN: 151926Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000564 AC: 131AN: 232466Hom.: 1 AF XY: 0.000528 AC XY: 66AN XY: 125040
GnomAD4 exome AF: 0.000128 AC: 185AN: 1450934Hom.: 1 Cov.: 31 AF XY: 0.000129 AC XY: 93AN XY: 720560
GnomAD4 genome AF: 0.000250 AC: 38AN: 152044Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19AN XY: 74326
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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not specified Benign:2
p.Ile451Ile in exon 8 of DES:This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 1.1% (43/3920) of Eas t Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broad institute.org; dbSNP rs121913002). -
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Desmin-related myofibrillar myopathy Benign:1
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Cardiomyopathy Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at