rs138016358
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001206927.2(DNAH8):āc.11182C>Gā(p.Pro3728Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000974 in 1,612,536 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P3728S) has been classified as Likely benign.
Frequency
Consequence
NM_001206927.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.11182C>G | p.Pro3728Ala | missense_variant | 75/93 | ENST00000327475.11 | |
DNAH8-AS1 | NR_038401.1 | n.161-4523G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.11182C>G | p.Pro3728Ala | missense_variant | 75/93 | 5 | NM_001206927.2 | P2 | |
DNAH8-AS1 | ENST00000416948.1 | n.153-4523G>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000660 AC: 10AN: 151498Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000558 AC: 14AN: 250880Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135568
GnomAD4 exome AF: 0.000101 AC: 147AN: 1461038Hom.: 1 Cov.: 31 AF XY: 0.0000894 AC XY: 65AN XY: 726786
GnomAD4 genome ? AF: 0.0000660 AC: 10AN: 151498Hom.: 0 Cov.: 31 AF XY: 0.0000541 AC XY: 4AN XY: 73960
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 13, 2023 | The c.11182C>G (p.P3728A) alteration is located in exon 75 (coding exon 74) of the DNAH8 gene. This alteration results from a C to G substitution at nucleotide position 11182, causing the proline (P) at amino acid position 3728 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces proline with alanine at codon 3728 of the DNAH8 protein (p.Pro3728Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs138016358, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with DNAH8-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: "Tolerated"; PolyPhen-2: "Not Available"; 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at