rs751953774
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001386795.1(DTNA):c.435G>A(p.Met145Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,604 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M145L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001386795.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTNA | NM_001386795.1 | c.435G>A | p.Met145Ile | missense_variant | 5/23 | ENST00000444659.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTNA | ENST00000444659.6 | c.435G>A | p.Met145Ile | missense_variant | 5/23 | 5 | NM_001386795.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251162Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135736
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461544Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727066
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74268
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 04, 2015 | The p.Met145Ile variant in DTNA has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/65872 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 751953774). Computational prediction tools and conservation analysis do not prov ide strong support for or against an impact to the protein. In summary, the clin ical significance of the p.Met145Ile variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at