rs560651490
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS1
The NM_015512.5(DNAH1):c.4353G>A(p.Glu1451=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00035 in 1,569,794 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00037 ( 4 hom. )
Consequence
DNAH1
NM_015512.5 synonymous
NM_015512.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.639
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 -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 3-52359332-G-A is Benign according to our data. Variant chr3-52359332-G-A is described in ClinVar as [Benign]. Clinvar id is 544641.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.639 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000151 (23/152304) while in subpopulation SAS AF= 0.00456 (22/4822). AF 95% confidence interval is 0.00309. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.4353G>A | p.Glu1451= | synonymous_variant | 26/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.4353G>A | p.Glu1451= | synonymous_variant | 27/80 | ||
DNAH1 | XM_017006130.2 | c.4353G>A | p.Glu1451= | synonymous_variant | 27/79 | ||
DNAH1 | XM_017006131.2 | c.4353G>A | p.Glu1451= | synonymous_variant | 27/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.4353G>A | p.Glu1451= | synonymous_variant | 26/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.4614G>A | non_coding_transcript_exon_variant | 26/77 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152186Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000910 AC: 165AN: 181272Hom.: 1 AF XY: 0.00129 AC XY: 126AN XY: 97468
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GnomAD4 exome AF: 0.000372 AC: 527AN: 1417490Hom.: 4 Cov.: 31 AF XY: 0.000566 AC XY: 397AN XY: 701178
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 15, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at