rs201309675
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015512.5(DNAH1):āc.9671A>Gā(p.Asn3224Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000586 in 1,553,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_015512.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.9671A>G | p.Asn3224Ser | missense_variant | 61/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.9740A>G | p.Asn3247Ser | missense_variant | 63/80 | ||
DNAH1 | XM_017006130.2 | c.9671A>G | p.Asn3224Ser | missense_variant | 62/79 | ||
DNAH1 | XM_017006131.2 | c.9614A>G | p.Asn3205Ser | missense_variant | 62/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.9671A>G | p.Asn3224Ser | missense_variant | 61/78 | 1 | NM_015512.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000388 AC: 59AN: 152120Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000497 AC: 8AN: 160892Hom.: 0 AF XY: 0.0000118 AC XY: 1AN XY: 84780
GnomAD4 exome AF: 0.0000236 AC: 33AN: 1400940Hom.: 0 Cov.: 32 AF XY: 0.0000188 AC XY: 13AN XY: 691106
GnomAD4 genome ? AF: 0.000381 AC: 58AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74442
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 04, 2019 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DNAH1-related disease. This variant is present in population databases (rs201309675, ExAC 0.2%). This sequence change replaces asparagine with serine at codon 3224 of the DNAH1 protein (p.Asn3224Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at