rs564134623
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001369.3(DNAH5):c.12694G>A(p.Asp4232Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000301 in 1,613,772 control chromosomes in the GnomAD database, including 3 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: 32)
Exomes 𝑓: 0.00032 ( 3 hom. )
Consequence
DNAH5
NM_001369.3 missense
NM_001369.3 missense
Scores
3
5
10
Clinical Significance
Conservation
PhyloP100: 6.17
Genes affected
DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0083580315).
BP6
Variant 5-13717326-C-T is Benign according to our data. Variant chr5-13717326-C-T is described in ClinVar as [Benign]. Clinvar id is 454738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000317 (463/1461450) while in subpopulation SAS AF= 0.00505 (435/86186). AF 95% confidence interval is 0.00466. There are 3 homozygotes in gnomad4_exome. There are 330 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.12694G>A | p.Asp4232Asn | missense_variant | 73/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.12694G>A | p.Asp4232Asn | missense_variant | 73/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.12649G>A | p.Asp4217Asn | missense_variant | 73/79 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152204Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000647 AC: 162AN: 250494Hom.: 3 AF XY: 0.000930 AC XY: 126AN XY: 135416
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GnomAD4 exome AF: 0.000317 AC: 463AN: 1461450Hom.: 3 Cov.: 32 AF XY: 0.000454 AC XY: 330AN XY: 727012
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GnomAD4 genome AF: 0.000151 AC: 23AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 01, 2017 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Benign
D
Polyphen
P
Vest4
MutPred
Loss of ubiquitination at K4235 (P = 0.0715);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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