3-52382437-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_015512.5(DNAH1):c.7923C>T(p.Phe2641=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000829 in 1,613,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00086 ( 0 hom. )
Consequence
DNAH1
NM_015512.5 synonymous
NM_015512.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.95
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.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 3-52382437-C-T is Benign according to our data. Variant chr3-52382437-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 544658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.95 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.7923C>T | p.Phe2641= | synonymous_variant | 50/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.7992C>T | p.Phe2664= | synonymous_variant | 52/80 | ||
DNAH1 | XM_017006130.2 | c.7923C>T | p.Phe2641= | synonymous_variant | 51/79 | ||
DNAH1 | XM_017006131.2 | c.7992C>T | p.Phe2664= | synonymous_variant | 52/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.7923C>T | p.Phe2641= | synonymous_variant | 50/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.8184C>T | non_coding_transcript_exon_variant | 50/77 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000512 AC: 78AN: 152244Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000558 AC: 139AN: 249056Hom.: 0 AF XY: 0.000585 AC XY: 79AN XY: 135130
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GnomAD4 exome AF: 0.000862 AC: 1260AN: 1461570Hom.: 0 Cov.: 32 AF XY: 0.000834 AC XY: 606AN XY: 727054
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GnomAD4 genome AF: 0.000512 AC: 78AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.000524 AC XY: 39AN XY: 74370
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
DNAH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 09, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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