9-34506825-CCTT-CCTTCTT

Position:

• chr9-34506825-CCTT-CCTTCTT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_012144.4(DNAI1):​c.1265_1267dupTCT​(p.Phe422dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAI1 NM_012144.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_012144.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAI1	NM_012144.4	c.1265_1267dupTCT	p.Phe422dup	disruptive_inframe_insertion	13/20	ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2	c.1277_1279dupTCT	p.Phe426dup	disruptive_inframe_insertion	13/20		NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9	c.1265_1267dupTCT	p.Phe422dup	disruptive_inframe_insertion	13/20	1	NM_012144.4	ENSP00000242317.4
DNAI1	ENST00000614641.4	c.1277_1279dupTCT	p.Phe426dup	disruptive_inframe_insertion	13/20	5		ENSP00000480538.1
DNAI1	ENST00000470169.5	n.200_202dupTCT		non_coding_transcript_exon_variant	1/6	5		ENSP00000434296.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs567346433; hg19: chr9-34506823;