rs3818577

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012144.4(DNAI1):c.378A>G(p.Glu126Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,613,670 control chromosomes in the GnomAD database, including 758 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 97 hom., cov: 32)

Exomes 𝑓: 0.010 ( 661 hom. )

Consequence

DNAI1
NM_012144.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.142

Publications

7 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: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-34489439-A-G is Benign according to our data. Variant chr9-34489439-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 163162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.142 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI1	NM_012144.4 link	c.378A>G	p.Glu126Glu	synonymous_variant	Exon 5 of 20	ENST00000242317.9	NP_036276.1	Q9UI46-1A0A140VJI0
DNAI1	NM_001281428.2 link	c.378A>G	p.Glu126Glu	synonymous_variant	Exon 5 of 20		NP_001268357.1	Q9UI46A0A087WWV9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAI1	ENST00000242317.9 link	c.378A>G	p.Glu126Glu	synonymous_variant	Exon 5 of 20	1	NM_012144.4	ENSP00000242317.4	Q9UI46-1
DNAI1	ENST00000614641.4 link	c.378A>G	p.Glu126Glu	synonymous_variant	Exon 5 of 20	5		ENSP00000480538.1	A0A087WWV9
DNAI1	ENST00000437363.5 link	c.345A>G	p.Glu115Glu	synonymous_variant	Exon 4 of 9	5		ENSP00000395396.1	Q5T8G8
DNAI1	ENST00000488369.1 link	n.494A>G		non_coding_transcript_exon_variant	Exon 5 of 9	3

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3334

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0398

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0433

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.0267

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.0210

GnomAD2 exomes

AF:

0.0325

AC:

8179

AN:

251476

AF XY:

0.0274

show subpopulations

Gnomad AFR exome

AF:

0.0402

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.00146

Gnomad OTH exome

AF:

0.0179

GnomAD4 exome

AF:

0.0102

AC:

14895

AN:

1461402

Hom.:

661

Cov.:

AF XY:

0.00992

AC XY:

7215

AN XY:

726996

show subpopulations

African (AFR)

AF:

0.0406

AC:

1360

AN:

33458

American (AMR)

AF:

0.101

AC:

4498

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26130

East Asian (EAS)

AF:

0.113

AC:

4483

AN:

39682

South Asian (SAS)

AF:

0.0236

AC:

2031

AN:

86232

European-Finnish (FIN)

AF:

0.0121

AC:

647

AN:

53390

Middle Eastern (MID)

AF:

0.0105

AC:

AN:

5532

European-Non Finnish (NFE)

AF:

0.000836

AC:

930

AN:

1111908

Other (OTH)

AF:

0.0147

AC:

885

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

926

1852

2778

3704

4630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0220

AC:

3355

AN:

152268

Hom.:

Cov.:

AF XY:

0.0230

AC XY:

1715

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0401

AC:

1667

AN:

41538

American (AMR)

AF:

0.0433

AC:

663

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.120

AC:

623

AN:

5178

South Asian (SAS)

AF:

0.0265

AC:

128

AN:

4832

European-Finnish (FIN)

AF:

0.0124

AC:

132

AN:

10612

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00129

AC:

AN:

68018

Other (OTH)

AF:

0.0213

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

163

325

488

650

813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.0285

Asia WGS

AF:

0.0760

AC:

262

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00184

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:4

Jun 19, 2014

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Glu126Glu in exon 5 of DNAI1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 4.0% (175/4406) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs3818577). -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Kartagener syndrome

Benign:1

Mar 06, 2017

Counsyl

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.0

(source)

DANN

Benign

0.29

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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rs3818577

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over