9-34506708-G-T

Position:

• chr9-34506708-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012144.4(DNAI1):​c.1145G>T​(p.Ser382Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNAI1 NM_012144.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAI1	NM_012144.4	c.1145G>T	p.Ser382Ile	missense_variant	13/20	ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2	c.1157G>T	p.Ser386Ile	missense_variant	13/20		NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9	c.1145G>T	p.Ser382Ile	missense_variant	13/20	1	NM_012144.4	ENSP00000242317.4
DNAI1	ENST00000614641.4	c.1157G>T	p.Ser386Ile	missense_variant	13/20	5		ENSP00000480538.1
DNAI1	ENST00000470169.5	n.80G>T		non_coding_transcript_exon_variant	1/6	5		ENSP00000434296.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251240 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135812

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.046	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.060
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	2.0	.;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.1	.;N
REVEL	Uncertain	0.45
Sift	Uncertain	0.011	.;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.031	.;B
Vest4		0.70
MutPred		0.55		.;Loss of disorder (P = 0.0068);
MVP		0.87
MPC		0.14
ClinPred		0.53	D
GERP RS		4.4
Varity_R		0.19
gMVP		0.57

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

LitVar

Other links and lift over

dbSNP: rs141690214; hg19: chr9-34506706;