17-11608140-C-T

Variant summary

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

The NM_001372.4(DNAH9):​c.429C>T​(p.Pro143Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,594,930 control chromosomes in the GnomAD database, including 145,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11811 hom., cov: 33)
Exomes 𝑓: 0.42 ( 134011 hom. )

Consequence

DNAH9
NM_001372.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.63
Variant links:
Genes affected
DNAH9 (HGNC:2953): (dynein axonemal heavy chain 9) This gene encodes the heavy chain subunit of axonemal dynein, a large multi-subunit molecular motor. Axonemal dynein attaches to microtubules and hydrolyzes ATP to mediate the movement of cilia and flagella. The gene expresses at least two transcript variants; additional variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 17-11608140-C-T is Benign according to our data. Variant chr17-11608140-C-T is described in ClinVar as [Benign]. Clinvar id is 402773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH9NM_001372.4 linkuse as main transcriptc.429C>T p.Pro143Pro synonymous_variant 2/69 ENST00000262442.9 NP_001363.2 Q9NYC9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH9ENST00000262442.9 linkuse as main transcriptc.429C>T p.Pro143Pro synonymous_variant 2/691 NM_001372.4 ENSP00000262442.3 Q9NYC9-1
DNAH9ENST00000579406.1 linkuse as main transcriptn.456C>T non_coding_transcript_exon_variant 2/81
DNAH9ENST00000454412.6 linkuse as main transcriptc.429C>T p.Pro143Pro synonymous_variant 2/685 ENSP00000414874.2 E7EP17
DNAH9ENST00000579828.5 linkuse as main transcriptc.429C>T p.Pro143Pro synonymous_variant 2/42 ENSP00000463782.1 J3QQK8

Frequencies

GnomAD3 genomes
AF:
0.373
AC:
56743
AN:
152006
Hom.:
11802
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.203
Gnomad AMI
AF:
0.344
Gnomad AMR
AF:
0.525
Gnomad ASJ
AF:
0.479
Gnomad EAS
AF:
0.549
Gnomad SAS
AF:
0.620
Gnomad FIN
AF:
0.382
Gnomad MID
AF:
0.535
Gnomad NFE
AF:
0.403
Gnomad OTH
AF:
0.422
GnomAD3 exomes
AF:
0.459
AC:
113315
AN:
246682
Hom.:
27974
AF XY:
0.463
AC XY:
61748
AN XY:
133274
show subpopulations
Gnomad AFR exome
AF:
0.197
Gnomad AMR exome
AF:
0.633
Gnomad ASJ exome
AF:
0.480
Gnomad EAS exome
AF:
0.542
Gnomad SAS exome
AF:
0.610
Gnomad FIN exome
AF:
0.379
Gnomad NFE exome
AF:
0.406
Gnomad OTH exome
AF:
0.454
GnomAD4 exome
AF:
0.422
AC:
609338
AN:
1442806
Hom.:
134011
Cov.:
34
AF XY:
0.427
AC XY:
304922
AN XY:
714354
show subpopulations
Gnomad4 AFR exome
AF:
0.191
Gnomad4 AMR exome
AF:
0.624
Gnomad4 ASJ exome
AF:
0.479
Gnomad4 EAS exome
AF:
0.584
Gnomad4 SAS exome
AF:
0.603
Gnomad4 FIN exome
AF:
0.377
Gnomad4 NFE exome
AF:
0.402
Gnomad4 OTH exome
AF:
0.431
GnomAD4 genome
AF:
0.373
AC:
56771
AN:
152124
Hom.:
11811
Cov.:
33
AF XY:
0.380
AC XY:
28287
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.203
Gnomad4 AMR
AF:
0.526
Gnomad4 ASJ
AF:
0.479
Gnomad4 EAS
AF:
0.549
Gnomad4 SAS
AF:
0.619
Gnomad4 FIN
AF:
0.382
Gnomad4 NFE
AF:
0.403
Gnomad4 OTH
AF:
0.423
Alfa
AF:
0.405
Hom.:
25846
Bravo
AF:
0.372
Asia WGS
AF:
0.559
AC:
1943
AN:
3478
EpiCase
AF:
0.417
EpiControl
AF:
0.420

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 28, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Ciliary dyskinesia, primary, 40 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.64
DANN
Benign
0.47

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.

Other links and lift over

dbSNP: rs11078022; hg19: chr17-11511457; COSMIC: COSV52339774; COSMIC: COSV52339774; API