rs185283741
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_001206927.2(DNAH8):c.11468C>T(p.Ala3823Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00058 in 1,611,272 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001206927.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.11468C>T | p.Ala3823Val | missense_variant | 77/93 | ENST00000327475.11 | |
DNAH8-AS1 | NR_038401.1 | n.160+691G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.11468C>T | p.Ala3823Val | missense_variant | 77/93 | 5 | NM_001206927.2 | P2 | |
DNAH8-AS1 | ENST00000416948.1 | n.152+691G>A | intron_variant, non_coding_transcript_variant | 2 | |||||
DNAH8 | ENST00000359357.7 | c.10817C>T | p.Ala3606Val | missense_variant | 75/91 | 2 | A2 | ||
DNAH8 | ENST00000449981.6 | c.11468C>T | p.Ala3823Val | missense_variant | 76/82 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000316 AC: 48AN: 151988Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000373 AC: 93AN: 249318Hom.: 1 AF XY: 0.000319 AC XY: 43AN XY: 134812
GnomAD4 exome AF: 0.000608 AC: 887AN: 1459166Hom.: 2 Cov.: 29 AF XY: 0.000544 AC XY: 395AN XY: 725864
GnomAD4 genome ? AF: 0.000316 AC: 48AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.000350 AC XY: 26AN XY: 74348
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill | Feb 03, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3823 of the DNAH8 protein (p.Ala3823Val). This variant is present in population databases (rs185283741, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. ClinVar contains an entry for this variant (Variation ID: 569635). 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 05, 2023 | The c.11468C>T (p.A3823V) alteration is located in exon 77 (coding exon 76) of the DNAH8 gene. This alteration results from a C to T substitution at nucleotide position 11468, causing the alanine (A) at amino acid position 3823 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Spermatogenic failure 46 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Johns Hopkins Genomics, Johns Hopkins University | Jan 19, 2021 | This DNAH8 variant (rs185283741) is present in a large population dataset (gnomAD: 102/280708 total alleles; 0.036%; no homozygotes) and has been reported in ClinVar. It has not been reported in the literature, to our knowledge. One bioinformatic tool queried predicts that this substitution would be tolerated, and the alanine residue at this position is poorly evolutionarily conserved across the species assessed. We consider the clinical significance of c.11432C>T to be uncertain at this time. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at