rs3818577

Positions:

chr9-34489439-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012144.4(DNAI1):c.378A>G(p.Glu126=) 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr9-34489439-A-G is described in Lovd as [Benign].

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/exons	MANE	UniProt
DNAI1	NM_012144.4 linkuse as main transcript	c.378A>G	p.Glu126=	synonymous_variant	5/20	ENST00000242317.9
DNAI1	NM_001281428.2 linkuse as main transcript	c.378A>G	p.Glu126=	synonymous_variant	5/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAI1	ENST00000242317.9 linkuse as main transcript	c.378A>G	p.Glu126=	synonymous_variant	5/20	1	NM_012144.4		Q9UI46-1
DNAI1	ENST00000614641.4 linkuse as main transcript	c.378A>G	p.Glu126=	synonymous_variant	5/20	5		P1
DNAI1	ENST00000437363.5 linkuse as main transcript	c.345A>G	p.Glu115=	synonymous_variant	4/9	5
DNAI1	ENST00000488369.1 linkuse as main transcript	n.494A>G		non_coding_transcript_exon_variant	5/9	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

GnomAD3 exomes

AF:

0.0325

AC:

8179

AN:

251476

Hom.:

438

AF XY:

0.0274

AC XY:

3719

AN XY:

135916

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 SAS exome

AF:

0.0250

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

Gnomad4 AFR exome

AF:

0.0406

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.113

Gnomad4 SAS exome

AF:

0.0236

Gnomad4 FIN exome

AF:

0.0121

Gnomad4 NFE exome

AF:

0.000836

Gnomad4 OTH exome

AF:

0.0147

GnomAD4 genome

AF:

0.0220

AC:

3355

AN:

152268

Hom.:

Cov.:

AF XY:

0.0230

AC XY:

1715

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0401

Gnomad4 AMR

AF:

0.0433

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.0265

Gnomad4 FIN

AF:

0.0124

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.00840

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jun 19, 2014	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. -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Kartagener syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Counsyl

Mar 06, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.0

DANN

Benign

0.29

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over