rs11793196

Variant names:

• chr9-34500823-G-A
• rs11793196
• NM_012144.4:c.1003G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-34500823-G-A
• chr9-34500823-G-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM5 BP4_Strong BP6_Very_Strong BA1

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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V335F) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: 𝑓 0.20 (3449 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17546 hom.)
• Consequence: DNAI1 NM_012144.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 7.61
• Publications: 24 publications found

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

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr9-34500823-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 525451.We mark this variant Likely_pathogenic, oryginal submission is: [Conflicting_classifications_of_pathogenicity].
• 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.
• 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 rank	MANE	Protein	UniProt
DNAI1	NM_012144.4	c.1003G>A	p.Val335Ile	missense_variant	Exon 11 of 20	ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2	c.1015G>A	p.Val339Ile	missense_variant	Exon 11 of 20		NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9	c.1003G>A	p.Val335Ile	missense_variant	Exon 11 of 20	1	NM_012144.4	ENSP00000242317.4
DNAI1	ENST00000614641.4	c.1015G>A	p.Val339Ile	missense_variant	Exon 11 of 20	5		ENSP00000480538.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29683 AN: 152068 Hom.: 3445 Cov.: 32

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

GnomAD2 exomes AF: 0.153 AC: 38388 AN: 251262 AF XY: 0.149

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 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.: 32 AF XY: 0.149 AC XY: 108235 AN XY: 726868

African (AFR) AF: 0.333 AC: 11152 AN: 33462

American (AMR) AF: 0.157 AC: 7008 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 5164 AN: 26132

East Asian (EAS) AF: 0.0129 AC: 511 AN: 39698

South Asian (SAS) AF: 0.150 AC: 12961 AN: 86250

European-Finnish (FIN) AF: 0.154 AC: 8205 AN: 53408

Middle Eastern (MID) AF: 0.166 AC: 952 AN: 5744

European-Non Finnish (NFE) AF: 0.146 AC: 162673 AN: 1111294

Other (OTH) AF: 0.157 AC: 9460 AN: 60358

GnomAD4 genome AF: 0.195 AC: 29714 AN: 152186 Hom.: 3449 Cov.: 32 AF XY: 0.192 AC XY: 14274 AN XY: 74414

African (AFR) AF: 0.327 AC: 13558 AN: 41498

American (AMR) AF: 0.163 AC: 2487 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3470

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5186

South Asian (SAS) AF: 0.144 AC: 692 AN: 4814

European-Finnish (FIN) AF: 0.147 AC: 1558 AN: 10612

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.149 AC: 10136 AN: 68010

Other (OTH) AF: 0.186 AC: 392 AN: 2112

Alfa AF: 0.159 Hom.: 8630

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

Submissions by phenotype

Primary ciliary dyskinesia Benign:4

Dec 11, 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. -

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:3

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

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). -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Kartagener syndrome Benign:2

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.75	T;T
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	.;M
PhyloP100		7.6
PrimateAI	Benign	0.38	T
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	T
GERP RS		5.0
Varity_R		0.083
gMVP		0.53
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11793196; hg19: chr9-34500821; COSMIC: COSV107285369;