rs76591348
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_015512.5(DNAH1):āc.1351A>Gā(p.Lys451Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00116 in 1,614,012 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.0010 ( 0 hom., cov: 33)
Exomes š: 0.0012 ( 6 hom. )
Consequence
DNAH1
NM_015512.5 missense
NM_015512.5 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 4.50
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.010901868).
BP6
?
Variant 3-52344554-A-G is Benign according to our data. Variant chr3-52344554-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 290747.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00117 (1716/1461674) while in subpopulation MID AF= 0.00433 (25/5768). AF 95% confidence interval is 0.00301. There are 6 homozygotes in gnomad4_exome. There are 876 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.1351A>G | p.Lys451Glu | missense_variant | 9/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.1351A>G | p.Lys451Glu | missense_variant | 10/80 | ||
DNAH1 | XM_017006130.2 | c.1351A>G | p.Lys451Glu | missense_variant | 10/79 | ||
DNAH1 | XM_017006131.2 | c.1351A>G | p.Lys451Glu | missense_variant | 10/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.1351A>G | p.Lys451Glu | missense_variant | 9/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.1612A>G | non_coding_transcript_exon_variant | 9/77 | 2 | ||||
DNAH1 | ENST00000497875.1 | n.1516A>G | non_coding_transcript_exon_variant | 10/21 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00105 AC: 160AN: 152220Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000967 AC: 241AN: 249242Hom.: 0 AF XY: 0.000991 AC XY: 134AN XY: 135204
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GnomAD4 exome AF: 0.00117 AC: 1716AN: 1461674Hom.: 6 Cov.: 31 AF XY: 0.00120 AC XY: 876AN XY: 727126
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GnomAD4 genome ? AF: 0.00104 AC: 159AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.000873 AC XY: 65AN XY: 74494
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ExAC
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 20, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 31, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 25, 2016 | - - |
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
DNAH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 04, 2021 | 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
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
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