9-34459027-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012144.4(DNAI1):c.22G>T(p.Ala8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 1,613,884 control chromosomes in the GnomAD database, including 3,592 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A8P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.050 ( 271 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3321 hom. )

Consequence

DNAI1
NM_012144.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.40

Publications

24 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016712248).

BP6

Variant 9-34459027-G-T is Benign according to our data. Variant chr9-34459027-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012144.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI1	NM_012144.4	MANE Select	c.22G>T	p.Ala8Ser	missense	Exon 1 of 20	NP_036276.1	A0A140VJI0
	DNAI1	NM_001281428.2		c.22G>T	p.Ala8Ser	missense	Exon 1 of 20	NP_001268357.1	A0A087WWV9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAI1	ENST00000242317.9	TSL:1 MANE Select	c.22G>T	p.Ala8Ser	missense	Exon 1 of 20	ENSP00000242317.4	Q9UI46-1
DNAI1	ENST00000878474.1		c.22G>T	p.Ala8Ser	missense	Exon 1 of 21	ENSP00000548533.1
DNAI1	ENST00000614641.4	TSL:5	c.22G>T	p.Ala8Ser	missense	Exon 1 of 20	ENSP00000480538.1	A0A087WWV9

Frequencies

GnomAD3 genomes

AF:

0.0496

AC:

7547

AN:

152090

Hom.:

271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0133

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0460

Gnomad ASJ

AF:

0.0473

Gnomad EAS

AF:

0.00789

Gnomad SAS

AF:

0.0448

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0651

Gnomad OTH

AF:

0.0392

GnomAD2 exomes

AF:

0.0550

AC:

13820

AN:

251398

AF XY:

0.0558

show subpopulations

Gnomad AFR exome

AF:

0.0124

Gnomad AMR exome

AF:

0.0439

Gnomad ASJ exome

AF:

0.0416

Gnomad EAS exome

AF:

0.00674

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.0625

Gnomad OTH exome

AF:

0.0611

GnomAD4 exome

AF:

0.0629

AC:

91923

AN:

1461676

Hom.:

3321

Cov.:

AF XY:

0.0627

AC XY:

45619

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.00995

AC:

333

AN:

33480

American (AMR)

AF:

0.0443

AC:

1981

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0419

AC:

1095

AN:

26136

East Asian (EAS)

AF:

0.00491

AC:

195

AN:

39700

South Asian (SAS)

AF:

0.0532

AC:

4586

AN:

86252

European-Finnish (FIN)

AF:

0.112

AC:

6002

AN:

53416

Middle Eastern (MID)

AF:

0.0331

AC:

191

AN:

5768

European-Non Finnish (NFE)

AF:

0.0667

AC:

74126

AN:

1111814

Other (OTH)

AF:

0.0565

AC:

3414

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

4568

9136

13705

18273

22841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2726

5452

8178

10904

13630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0496

AC:

7546

AN:

152208

Hom.:

271

Cov.:

AF XY:

0.0505

AC XY:

3758

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0133

AC:

552

AN:

41546

American (AMR)

AF:

0.0461

AC:

704

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0473

AC:

164

AN:

3470

East Asian (EAS)

AF:

0.00772

AC:

AN:

5184

South Asian (SAS)

AF:

0.0448

AC:

216

AN:

4822

European-Finnish (FIN)

AF:

0.118

AC:

1251

AN:

10602

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0650

AC:

4422

AN:

67980

Other (OTH)

AF:

0.0393

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

363

726

1090

1453

1816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0488

Hom.:

306

Bravo

AF:

0.0413

TwinsUK

AF:

0.0693

AC:

257

ALSPAC

AF:

0.0701

AC:

270

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.0630

AC:

542

ExAC

AF:

0.0540

AC:

6553

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.0614

EpiControl

AF:

0.0563

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (4)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.7

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0076

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

2.4

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.44

REVEL

Benign

0.16

Sift

Benign

0.40

Sift4G

Benign

0.70

Polyphen

0.0020

Vest4

0.080

MPC

0.10

ClinPred

0.012

GERP RS

2.6

PromoterAI

0.0057

Neutral

(source)

Varity_R

0.043

gMVP

0.093

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over