rs140937135
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001206927.2(DNAH8):āc.11851A>Gā(p.Thr3951Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,611,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. T3951T) has been classified as Benign.
Frequency
Consequence
NM_001206927.2 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 |
---|---|---|---|---|---|---|---|
DNAH8 | NM_001206927.2 | c.11851A>G | p.Thr3951Ala | missense_variant | 79/93 | ENST00000327475.11 | |
DNAH8-AS1 | NR_038401.1 | n.61-2440T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH8 | ENST00000327475.11 | c.11851A>G | p.Thr3951Ala | missense_variant | 79/93 | 5 | NM_001206927.2 | P2 | |
DNAH8-AS1 | ENST00000416948.1 | n.53-2440T>C | intron_variant, non_coding_transcript_variant | 2 | |||||
DNAH8 | ENST00000359357.7 | c.11200A>G | p.Thr3734Ala | missense_variant | 77/91 | 2 | A2 | ||
DNAH8 | ENST00000449981.6 | c.11851A>G | p.Thr3951Ala | missense_variant | 78/82 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000152 AC: 38AN: 249306Hom.: 0 AF XY: 0.000141 AC XY: 19AN XY: 134770
GnomAD4 exome AF: 0.000232 AC: 338AN: 1459596Hom.: 0 Cov.: 30 AF XY: 0.000234 AC XY: 170AN XY: 726086
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74364
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 23, 2022 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 3951 of the DNAH8 protein (p.Thr3951Ala). This variant is present in population databases (rs140937135, gnomAD 0.03%). 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: 575344). 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