9-34514428-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012144.4(DNAI1):ā€‹c.1604C>Gā€‹(p.Thr535Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

DNAI1
NM_012144.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.67
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAI1NM_012144.4 linkc.1604C>G p.Thr535Ser missense_variant Exon 17 of 20 ENST00000242317.9 NP_036276.1 Q9UI46-1A0A140VJI0
DNAI1NM_001281428.2 linkc.1616C>G p.Thr539Ser missense_variant Exon 17 of 20 NP_001268357.1 Q9UI46A0A087WWV9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAI1ENST00000242317.9 linkc.1604C>G p.Thr535Ser missense_variant Exon 17 of 20 1 NM_012144.4 ENSP00000242317.4 Q9UI46-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461882
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.10
T;T
Eigen
Benign
-0.13
Eigen_PC
Benign
0.045
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.78
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.1
.;L
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-2.9
.;D
REVEL
Benign
0.098
Sift
Benign
0.083
.;T
Sift4G
Benign
0.13
T;T
Polyphen
0.0010
.;B
Vest4
0.27
MutPred
0.56
.;Gain of disorder (P = 0.025);
MVP
0.78
MPC
0.10
ClinPred
0.17
T
GERP RS
4.6
Varity_R
0.19
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.26
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.26
Position offset: 1

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.

Other links and lift over

dbSNP: rs76334696; hg19: chr9-34514426; API