Variant 9-34514428-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The ENST00000242317.9(DNAI1):c.1604C>G(p.Thr535Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T535N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DNAI1
ENST00000242317.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.67

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a repeat WD 5 (size 39) in uniprot entity DNAI1_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in ENST00000242317.9

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 linkuse as main transcript	c.1604C>G	p.Thr535Ser	missense_variant	17/20	ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2 linkuse as main transcript	c.1616C>G	p.Thr539Ser	missense_variant	17/20		NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9 linkuse as main transcript	c.1604C>G	p.Thr535Ser	missense_variant	17/20	1	NM_012144.4	ENSP00000242317		Q9UI46-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

show subpopulations

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

0.045

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

.;L

MutationTaster

Benign

0.78

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.9

.;D

REVEL

Benign

0.098

Sift

Benign

0.083

.;T

Sift4G

Benign

0.13

T;T

Polyphen

0.0010

.;B

Vest4

0.27

MutPred

0.56

.;Gain of disorder (P = 0.025);

MVP

0.78

MPC

0.10

ClinPred

0.17

GERP RS

4.6

Varity_R

0.19

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.26

Position offset: 1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over