rs567346433
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2
The NM_012144.4(DNAI1):βc.1265_1267delβ(p.Phe422del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000436 in 1,614,180 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (β β ).
Frequency
Genomes: π 0.0022 ( 2 hom., cov: 32)
Exomes π: 0.00026 ( 0 hom. )
Consequence
DNAI1
NM_012144.4 inframe_deletion
NM_012144.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.68
Genes affected
DNAI1 (HGNC:2954): (dynein axonemal intermediate chain 1) This gene encodes a member of the dynein intermediate chain family. The encoded protein is part of the dynein complex in respiratory cilia. The inner- and outer-arm dyneins, which bridge between the doublet microtubules in axonemes, are the force-generating proteins responsible for the sliding movement in axonemes. The intermediate and light chains, thought to form the base of the dynein arm, help mediate attachment and may also participate in regulating dynein activity. Mutations in this gene result in abnormal ciliary ultrastructure and function associated with primary ciliary dyskinesia and Kartagener syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_012144.4. Strenght limited to Supporting due to length of the change: 1aa.
BP6
?
Variant 9-34506825-CCTT-C is Benign according to our data. Variant chr9-34506825-CCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 454827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00216 (329/152332) while in subpopulation AFR AF= 0.00715 (297/41566). AF 95% confidence interval is 0.00648. There are 2 homozygotes in gnomad4. There are 156 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAI1 | NM_012144.4 | c.1265_1267del | p.Phe422del | inframe_deletion | 13/20 | ENST00000242317.9 | |
DNAI1 | NM_001281428.2 | c.1277_1279del | p.Phe426del | inframe_deletion | 13/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAI1 | ENST00000242317.9 | c.1265_1267del | p.Phe422del | inframe_deletion | 13/20 | 1 | NM_012144.4 | ||
DNAI1 | ENST00000614641.4 | c.1277_1279del | p.Phe426del | inframe_deletion | 13/20 | 5 | P1 | ||
DNAI1 | ENST00000470169.5 | c.202_204del | p.Phe68del | inframe_deletion, NMD_transcript_variant | 1/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00214 AC: 325AN: 152214Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000606 AC: 152AN: 250952Hom.: 0 AF XY: 0.000509 AC XY: 69AN XY: 135658
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GnomAD4 exome AF: 0.000256 AC: 374AN: 1461848Hom.: 0 AF XY: 0.000243 AC XY: 177AN XY: 727232
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 24, 2023 | This alteration is classified as likely 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | DNAI1: BS1 - |
Kartagener syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Mar 27, 2017 | - - |
Computational scores
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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