rs199560640
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015512.5(DNAH1):āc.9638A>Gā(p.Asn3213Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,551,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. N3213N) 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.9638A>G | p.Asn3213Ser | missense_variant | 61/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.9707A>G | p.Asn3236Ser | missense_variant | 63/80 | ||
DNAH1 | XM_017006130.2 | c.9638A>G | p.Asn3213Ser | missense_variant | 62/79 | ||
DNAH1 | XM_017006131.2 | c.9581A>G | p.Asn3194Ser | missense_variant | 62/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.9638A>G | p.Asn3213Ser | missense_variant | 61/78 | 1 | NM_015512.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000243 AC: 37AN: 152164Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000183 AC: 29AN: 158646Hom.: 0 AF XY: 0.0000957 AC XY: 8AN XY: 83558
GnomAD4 exome AF: 0.000215 AC: 301AN: 1399710Hom.: 0 Cov.: 32 AF XY: 0.000181 AC XY: 125AN XY: 690378
GnomAD4 genome ? AF: 0.000243 AC: 37AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.000296 AC XY: 22AN XY: 74336
ClinVar
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 03, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 3213 of the DNAH1 protein (p.Asn3213Ser). This variant is present in population databases (rs199560640, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of primary ciliary dyskinesia (Invitae). ClinVar contains an entry for this variant (Variation ID: 478515). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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