3-52386175-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_015512.5(DNAH1):c.8641G>A(p.Ala2881Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,613,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A2881S) has been classified as Uncertain significance.
Frequency
Consequence
NM_015512.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.8641G>A | p.Ala2881Thr | missense_variant | 55/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.8710G>A | p.Ala2904Thr | missense_variant | 57/80 | ||
DNAH1 | XM_017006130.2 | c.8641G>A | p.Ala2881Thr | missense_variant | 56/79 | ||
DNAH1 | XM_017006131.2 | c.8710G>A | p.Ala2904Thr | missense_variant | 57/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.8641G>A | p.Ala2881Thr | missense_variant | 55/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.8902G>A | non_coding_transcript_exon_variant | 55/77 | 2 | ||||
DNAH1 | ENST00000488988.5 | n.231G>A | non_coding_transcript_exon_variant | 3/25 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152284Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000443 AC: 11AN: 248100Hom.: 0 AF XY: 0.0000520 AC XY: 7AN XY: 134694
GnomAD4 exome AF: 0.0000849 AC: 124AN: 1460836Hom.: 0 Cov.: 31 AF XY: 0.0000826 AC XY: 60AN XY: 726658
GnomAD4 genome AF: 0.0000459 AC: 7AN: 152402Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74526
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces alanine with threonine at codon 2881 of the DNAH1 protein (p.Ala2881Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs370257194, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.8641G>A (p.A2881T) alteration is located in exon 55 (coding exon 54) of the DNAH1 gene. This alteration results from a G to A substitution at nucleotide position 8641, causing the alanine (A) at amino acid position 2881 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at