9-34489427-T-C

Position:

• chr9-34489427-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_012144.4(DNAI1):​c.366T>C​(p.His122His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAI1 NM_012144.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.358

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]

DNAI1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 9-34489427-T-C is Benign according to our data. Variant chr9-34489427-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1543623.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.358 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAI1	NM_012144.4	c.366T>C	p.His122His	synonymous_variant	5/20	ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2	c.366T>C	p.His122His	synonymous_variant	5/20		NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9	c.366T>C	p.His122His	synonymous_variant	5/20	1	NM_012144.4	ENSP00000242317.4
DNAI1	ENST00000614641.4	c.366T>C	p.His122His	synonymous_variant	5/20	5		ENSP00000480538.1
DNAI1	ENST00000437363.5	c.333T>C	p.His111His	synonymous_variant	4/9	5		ENSP00000395396.1
DNAI1	ENST00000488369.1	n.482T>C		non_coding_transcript_exon_variant	5/9	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.4
DANN	Benign	0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-34489425;