chr9-34459001-TTGAGA-T
Position:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_012144.4(DNAI1):c.-1_4del variant causes a start lost, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
DNAI1
NM_012144.4 start_lost, 5_prime_UTR
NM_012144.4 start_lost, 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.66
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 Pathogenic. Variant got 12 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 9-34459001-TTGAGA-T is Pathogenic according to our data. Variant chr9-34459001-TTGAGA-T is described in ClinVar as [Pathogenic]. Clinvar id is 2026405.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAI1 | NM_012144.4 | c.-1_4del | start_lost, 5_prime_UTR_variant | 1/20 | ENST00000242317.9 | ||
DNAI1 | NM_001281428.2 | c.-1_4del | start_lost, 5_prime_UTR_variant | 1/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAI1 | ENST00000242317.9 | c.-1_4del | start_lost, 5_prime_UTR_variant | 1/20 | 1 | NM_012144.4 | |||
DNAI1 | ENST00000437363.5 | c.-1_4del | start_lost, 5_prime_UTR_variant | 1/9 | 5 | ||||
DNAI1 | ENST00000614641.4 | c.-1_4del | start_lost, 5_prime_UTR_variant | 1/20 | 5 | P1 | |||
DNAI1 | ENST00000470982.5 | n.47+1545_47+1549del | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the DNAI1 mRNA. The next in-frame methionine is located at codon 178. This variant has not been reported in the literature in individuals affected with DNAI1-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the DNAI1 protein in which other variant(s) (p.Arg124Cys) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.