rs11999454

Positions:

chr9-34512395-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012144.4(DNAI1):c.1460T>G(p.Val487Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0127 in 1,614,028 control chromosomes in the GnomAD database, including 846 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 139 hom., cov: 32)

Exomes 𝑓: 0.011 ( 707 hom. )

Consequence

DNAI1
NM_012144.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.84

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001478523).

BP6

Variant 9-34512395-T-G is Benign according to our data. Variant chr9-34512395-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 163165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-34512395-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAI1	NM_012144.4 linkuse as main transcript	c.1460T>G	p.Val487Gly	missense_variant	15/20	ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2 linkuse as main transcript	c.1472T>G	p.Val491Gly	missense_variant	15/20		NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9 linkuse as main transcript	c.1460T>G	p.Val487Gly	missense_variant	15/20	1	NM_012144.4	ENSP00000242317		Q9UI46-1
DNAI1	ENST00000614641.4 linkuse as main transcript	c.1472T>G	p.Val491Gly	missense_variant	15/20	5		ENSP00000480538	P1
DNAI1	ENST00000470169.5 linkuse as main transcript	c.398T>G	p.Val133Gly	missense_variant, NMD_transcript_variant	3/6	5		ENSP00000434296

Frequencies

GnomAD3 genomes

AF:

0.0282

AC:

4294

AN:

152036

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0608

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0463

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0274

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0344

AC:

8656

AN:

251300

Hom.:

456

AF XY:

0.0290

AC XY:

3935

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.0644

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.131

Gnomad SAS exome

AF:

0.0248

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.00184

Gnomad OTH exome

AF:

0.0191

GnomAD4 exome

AF:

0.0110

AC:

16142

AN:

1461874

Hom.:

707

Cov.:

AF XY:

0.0107

AC XY:

7789

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0650

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.113

Gnomad4 SAS exome

AF:

0.0234

Gnomad4 FIN exome

AF:

0.0121

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0283

AC:

4310

AN:

152154

Hom.:

139

Cov.:

AF XY:

0.0290

AC XY:

2158

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0610

Gnomad4 AMR

AF:

0.0464

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.0270

Gnomad4 FIN

AF:

0.0125

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0121

Hom.:

123

Bravo

AF:

0.0363

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.0611

AC:

269

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.0328

AC:

3978

Asia WGS

AF:

0.0770

AC:

265

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00231

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	Ambry Genetics	Jan 12, 2015	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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Val487Gly in exon 15 of DNAI1: This variant is not expected to have clinical sig nificance because it has been identified in 6.1% (269/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs11999454). -

not provided

Benign:2

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

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

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0033

T;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.40

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.7

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

4.3

.;N

REVEL

Benign

0.19

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.023

MPC

0.15

ClinPred

0.00073

GERP RS

3.5

Varity_R

0.042

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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