rs140768365
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001386795.1(DTNA):c.316C>G(p.Gln106Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,614,176 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q106L) 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTNA | NM_001386795.1 | c.316C>G | p.Gln106Glu | missense_variant | 4/23 | ENST00000444659.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTNA | ENST00000444659.6 | c.316C>G | p.Gln106Glu | missense_variant | 4/23 | 5 | NM_001386795.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 152220Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000203 AC: 51AN: 251328Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135832
GnomAD4 exome AF: 0.000209 AC: 305AN: 1461838Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 137AN XY: 727226
GnomAD4 genome ? AF: 0.000236 AC: 36AN: 152338Hom.: 1 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74492
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 10, 2014 | The Gln106Glu variant in DTNA has not been previously reported in individuals wi th cardiomyopathy, but has been identified in 2/8600 European American chromosom es by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbS NP rs140768365). Computational prediction tools do not provide strong support fo r or against an impact to the protein. In summary, the clinical significance of the Gln106Glu variant is uncertain. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 31, 2023 | The c.316C>G (p.Q106E) alteration is located in exon 4 (coding exon 3) of the DTNA gene. This alteration results from a C to G substitution at nucleotide position 316, causing the glutamine (Q) at amino acid position 106 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
See cases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations | Nov 18, 2020 | We observed the c.316C>G (p.Q106E) genetic variant in a 57-y.o. male proband diagnosed with left ventricular non-compaction and dilated cardiomyopathy. The p.Q106E genetic variant is present in gnomAD database, its frequency is 2.051e-4. Online in silico tools predict genetic variant p.Q106E to be probably pathogenic. No functional studies are available to date; family DNA samples were likewise unavailable for segregation analysis, therefore, we could only classify the p.Q106E genetic variant as a variant of uncertain clinical significance. - |
Left ventricular noncompaction 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 106 of the DTNA protein (p.Gln106Glu). This variant is present in population databases (rs140768365, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with DTNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 178033). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DTNA protein function with a negative predictive value of 80%. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at