rs200707455
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015512.5(DNAH1):āc.3380A>Gā(p.Asn1127Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,613,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_015512.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.3380A>G | p.Asn1127Ser | missense_variant | 20/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.3380A>G | p.Asn1127Ser | missense_variant | 21/80 | ||
DNAH1 | XM_017006130.2 | c.3380A>G | p.Asn1127Ser | missense_variant | 21/79 | ||
DNAH1 | XM_017006131.2 | c.3380A>G | p.Asn1127Ser | missense_variant | 21/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.3380A>G | p.Asn1127Ser | missense_variant | 20/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.3641A>G | non_coding_transcript_exon_variant | 20/77 | 2 | ||||
DNAH1 | ENST00000497875.1 | n.3545A>G | non_coding_transcript_exon_variant | 21/21 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000442 AC: 11AN: 248822Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135050
GnomAD4 exome AF: 0.0000677 AC: 99AN: 1461524Hom.: 0 Cov.: 31 AF XY: 0.0000688 AC XY: 50AN XY: 727042
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 07, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1127 of the DNAH1 protein (p.Asn1127Ser). This variant is present in population databases (rs200707455, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 478440). 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: "Benign"; 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 22, 2023 | The c.3380A>G (p.N1127S) alteration is located in exon 20 (coding exon 19) of the DNAH1 gene. This alteration results from a A to G substitution at nucleotide position 3380, causing the asparagine (N) at amino acid position 1127 to be replaced by a serine (S). 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