rs75513160
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_015512.5(DNAH1):c.10305G>A(p.Thr3435=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,597,196 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.015 ( 64 hom., cov: 29)
Exomes 𝑓: 0.0019 ( 66 hom. )
Consequence
DNAH1
NM_015512.5 synonymous
NM_015512.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.32
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 Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 3-52392856-G-A is Benign according to our data. Variant chr3-52392856-G-A is described in ClinVar as [Benign]. Clinvar id is 478377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
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Synonymous conserved (PhyloP=-1.32 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.10305G>A | p.Thr3435= | synonymous_variant | 65/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.10374G>A | p.Thr3458= | synonymous_variant | 67/80 | ||
DNAH1 | XM_017006130.2 | c.10305G>A | p.Thr3435= | synonymous_variant | 66/79 | ||
DNAH1 | XM_017006131.2 | c.10248G>A | p.Thr3416= | synonymous_variant | 66/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.10305G>A | p.Thr3435= | synonymous_variant | 65/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.10762G>A | non_coding_transcript_exon_variant | 64/77 | 2 | ||||
DNAH1 | ENST00000488988.5 | n.2091G>A | non_coding_transcript_exon_variant | 12/25 | 2 | ||||
DNAH1 | ENST00000490713.5 | c.1005G>A | p.Thr335= | synonymous_variant, NMD_transcript_variant | 8/20 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0154 AC: 2205AN: 143144Hom.: 64 Cov.: 29
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GnomAD3 exomes AF: 0.00391 AC: 969AN: 247530Hom.: 30 AF XY: 0.00282 AC XY: 379AN XY: 134388
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GnomAD4 exome AF: 0.00189 AC: 2742AN: 1453972Hom.: 66 Cov.: 39 AF XY: 0.00165 AC XY: 1190AN XY: 721488
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GnomAD4 genome ? AF: 0.0154 AC: 2211AN: 143224Hom.: 64 Cov.: 29 AF XY: 0.0148 AC XY: 1021AN XY: 68876
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2020 | - - |
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at