chr18-34851850-G-C
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001386795.1(DTNA):āc.1454G>Cā(p.Ser485Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 1,614,060 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S485I) has been classified as Uncertain significance.
Frequency
Consequence
NM_001386795.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTNA | NM_001386795.1 | c.1454G>C | p.Ser485Thr | missense_variant | 15/23 | ENST00000444659.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTNA | ENST00000444659.6 | c.1454G>C | p.Ser485Thr | missense_variant | 15/23 | 5 | NM_001386795.1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000541 AC: 136AN: 251168Hom.: 1 AF XY: 0.000361 AC XY: 49AN XY: 135732
GnomAD4 exome AF: 0.0000971 AC: 142AN: 1461716Hom.: 1 Cov.: 31 AF XY: 0.0000729 AC XY: 53AN XY: 727176
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6AN XY: 74504
ClinVar
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 10, 2020 | Variant summary: DTNA c.1373G>C (p.Ser458Thr) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00054 in 251168 control chromosomes, predominantly at a frequency of 0.0039 within the Latino subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 1248-fold of the estimated maximal expected allele frequency for a pathogenic variant in DTNA causing Left Ventricular Noncompaction phenotype (3.1e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.1373G>C in individuals affected with Left Ventricular Noncompaction and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 05, 2020 | - - |
DTNA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 14, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Left ventricular noncompaction 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at