rs11793196

Positions:

Variant summary

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

The NM_012144.4(DNAI1):c.1003G>A(p.Val335Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,613,248 control chromosomes in the GnomAD database, including 20,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3449 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17546 hom. )

Consequence

DNAI1
NM_012144.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 7.61

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=0.0015288591).

BP6

Variant 9-34500823-G-A is Benign according to our data. Variant chr9-34500823-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 163164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-34500823-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAI1	NM_012144.4 link	c.1003G>A	p.Val335Ile	missense_variant	11/20	ENST00000242317.9	NP_036276.1	Q9UI46-1A0A140VJI0
DNAI1	NM_001281428.2 link	c.1015G>A	p.Val339Ile	missense_variant	11/20		NP_001268357.1	Q9UI46A0A087WWV9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9 link	c.1003G>A	p.Val335Ile	missense_variant	11/20	1	NM_012144.4	ENSP00000242317.4		Q9UI46-1
DNAI1	ENST00000614641.4 link	c.1015G>A	p.Val339Ile	missense_variant	11/20	5		ENSP00000480538.1		A0A087WWV9

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29683

AN:

152068

Hom.:

3445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.0114

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.185

GnomAD3 exomes

AF:

0.153

AC:

38388

AN:

251262

Hom.:

3459

AF XY:

0.149

AC XY:

20211

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.00886

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.149

AC:

218086

AN:

1461062

Hom.:

17546

Cov.:

AF XY:

0.149

AC XY:

108235

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.333

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.198

Gnomad4 EAS exome

AF:

0.0129

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.146

Gnomad4 OTH exome

AF:

0.157

GnomAD4 genome

AF:

0.195

AC:

29714

AN:

152186

Hom.:

3449

Cov.:

AF XY:

0.192

AC XY:

14274

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.327

Gnomad4 AMR

AF:

0.163

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.0114

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.149

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.149

Hom.:

4802

Bravo

AF:

0.202

TwinsUK

AF:

0.144

AC:

535

ALSPAC

AF:

0.153

AC:

591

ESP6500AA

AF:

0.322

AC:

1420

ESP6500EA

AF:

0.152

AC:

1308

ExAC

AF:

0.156

AC:

18945

Asia WGS

AF:

0.108

AC:

375

AN:

3478

EpiCase

AF:

0.148

EpiControl

AF:

0.149

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

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	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Dec 11, 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. -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Val335Ile in exon 11 of DNAI1: This variant is not expected to have clinical sig nificance because it has been identified in 32.2% (1420/4406) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs11793196). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
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 27, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Kartagener syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

T;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

2.9

.;M

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.92

.;N

REVEL

Benign

0.23

Sift

Benign

0.089

.;T

Sift4G

Uncertain

0.036

D;D

Polyphen

0.19

.;B

Vest4

0.17

MPC

0.10

ClinPred

0.052

GERP RS

5.0

Varity_R

0.083

gMVP

0.53

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

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