Genetic Variant DNAI1:p.Glu673Asp (chr9-34520675-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012144.4(DNAI1):c.2019G>T(p.Glu673Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E673E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

DNAI1
NM_012144.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17264017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI1	NM_012144.4 link	c.2019G>T	p.Glu673Asp	missense_variant	Exon 20 of 20	ENST00000242317.9	NP_036276.1	Q9UI46-1A0A140VJI0
DNAI1	NM_001281428.2 link	c.2031G>T	p.Glu677Asp	missense_variant	Exon 20 of 20		NP_001268357.1	Q9UI46A0A087WWV9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAI1	ENST00000242317.9 link	c.2019G>T	p.Glu673Asp	missense_variant	Exon 20 of 20	1	NM_012144.4	ENSP00000242317.4	Q9UI46-1
DNAI1	ENST00000614641.4 link	c.2031G>T	p.Glu677Asp	missense_variant	Exon 20 of 20	5		ENSP00000480538.1	A0A087WWV9
DNAI1	ENST00000442556.1 link	c.345G>T	p.Glu115Asp	missense_variant	Exon 4 of 4	5		ENSP00000408129.1	H0Y6V0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399372

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00

AC:

AN:

79232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078956

Other (OTH)

AF:

0.00

AC:

AN:

58000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.028

T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.3

.;L

PhyloP100

1.4

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.2

.;N

REVEL

Benign

0.25

Sift

Benign

0.36

.;T

Sift4G

Benign

0.49

T;T

Polyphen

0.014

.;B

Vest4

0.23

MutPred

0.21

.;Loss of methylation at K676 (P = 0.1127);

MVP

0.82

MPC

0.10

ClinPred

0.20

GERP RS

0.49

Varity_R

0.075

gMVP

0.27

Mutation Taster

=90/10

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over