rs1553628078
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015512.5(DNAH1):c.1003C>G(p.Pro335Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P335S) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
DNAH1
NM_015512.5 missense
NM_015512.5 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: 4.26
Genes affected
DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.1003C>G | p.Pro335Ala | missense_variant | 7/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.1003C>G | p.Pro335Ala | missense_variant | 8/80 | ||
DNAH1 | XM_017006130.2 | c.1003C>G | p.Pro335Ala | missense_variant | 8/79 | ||
DNAH1 | XM_017006131.2 | c.1003C>G | p.Pro335Ala | missense_variant | 8/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.1003C>G | p.Pro335Ala | missense_variant | 7/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.1264C>G | non_coding_transcript_exon_variant | 7/77 | 2 | ||||
DNAH1 | ENST00000497875.1 | n.1168C>G | non_coding_transcript_exon_variant | 8/21 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2018 | 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. 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"). This variant has not been reported in the literature in individuals with DNAH1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 335 of the DNAH1 protein (p.Pro335Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MutPred
Gain of helix (P = 0.027);
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -22
Find out detailed SpliceAI scores and Pangolin per-transcript scores at