rs369765657
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015512.5(DNAH1):c.9914C>A(p.Thr3305Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,611,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T3305T) has been classified as Likely benign.
Frequency
Consequence
NM_015512.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.9914C>A | p.Thr3305Lys | missense_variant | 63/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.9983C>A | p.Thr3328Lys | missense_variant | 65/80 | ||
DNAH1 | XM_017006130.2 | c.9914C>A | p.Thr3305Lys | missense_variant | 64/79 | ||
DNAH1 | XM_017006131.2 | c.9857C>A | p.Thr3286Lys | missense_variant | 64/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.9914C>A | p.Thr3305Lys | missense_variant | 63/78 | 1 | NM_015512.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152068Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000490 AC: 12AN: 244804Hom.: 0 AF XY: 0.0000376 AC XY: 5AN XY: 132818
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1459678Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 725976
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152068Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74256
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2023 | The c.9914C>A (p.T3305K) alteration is located in exon 63 (coding exon 62) of the DNAH1 gene. This alteration results from a C to A substitution at nucleotide position 9914, causing the threonine (T) at amino acid position 3305 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 478519). This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. This variant is present in population databases (rs369765657, gnomAD 0.009%). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 3305 of the DNAH1 protein (p.Thr3305Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at