rs113529103
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_015512.5(DNAH1):c.7848C>T(p.Tyr2616=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 1,613,994 control chromosomes in the GnomAD database, including 174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.018 ( 74 hom., cov: 33)
Exomes 𝑓: 0.0021 ( 100 hom. )
Consequence
DNAH1
NM_015512.5 synonymous
NM_015512.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.40
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant 3-52382362-C-T is Benign according to our data. Variant chr3-52382362-C-T is described in ClinVar as [Benign]. Clinvar id is 478495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.39 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.7848C>T | p.Tyr2616= | synonymous_variant | 50/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.7917C>T | p.Tyr2639= | synonymous_variant | 52/80 | ||
DNAH1 | XM_017006130.2 | c.7848C>T | p.Tyr2616= | synonymous_variant | 51/79 | ||
DNAH1 | XM_017006131.2 | c.7917C>T | p.Tyr2639= | synonymous_variant | 52/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.7848C>T | p.Tyr2616= | synonymous_variant | 50/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.8109C>T | non_coding_transcript_exon_variant | 50/77 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0184 AC: 2801AN: 152184Hom.: 74 Cov.: 33
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GnomAD3 exomes AF: 0.00485 AC: 1210AN: 249244Hom.: 37 AF XY: 0.00399 AC XY: 539AN XY: 135214
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GnomAD4 exome AF: 0.00207 AC: 3026AN: 1461692Hom.: 100 Cov.: 32 AF XY: 0.00181 AC XY: 1316AN XY: 727134
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GnomAD4 genome ? AF: 0.0184 AC: 2805AN: 152302Hom.: 74 Cov.: 33 AF XY: 0.0180 AC XY: 1338AN XY: 74474
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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 | GeneDx | Jul 09, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 16, 2023 | - - |
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 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