NM_001372.4:c.3369T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001372.4(DNAH9):c.3369T>C(p.Asp1123Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 1,613,704 control chromosomes in the GnomAD database, including 776,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71261 hom., cov: 32)

Exomes 𝑓: 0.98 ( 704758 hom. )

Consequence

DNAH9
NM_001372.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.277

Publications

16 publications found

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]

DNAH9 Gene-Disease associations (from GenCC):

ciliary dyskinesia, primary, 40
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
situs inversus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
schizophrenia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

DNAH9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-11679772-T-C is Benign according to our data. Variant chr17-11679772-T-C is described in ClinVar as Benign. ClinVar VariationId is 402776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.277 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4 link	c.3369T>C	p.Asp1123Asp	synonymous_variant	Exon 18 of 69	ENST00000262442.9	NP_001363.2	Q9NYC9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9 link	c.3369T>C	p.Asp1123Asp	synonymous_variant	Exon 18 of 69	1	NM_001372.4	ENSP00000262442.3		Q9NYC9-1
DNAH9	ENST00000454412.6 link	c.3369T>C	p.Asp1123Asp	synonymous_variant	Exon 18 of 68	5		ENSP00000414874.2		E7EP17

Frequencies

GnomAD3 genomes

AF:

0.967

AC:

147142

AN:

152156

Hom.:

71210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.929

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.971

Gnomad ASJ

AF:

0.969

Gnomad EAS

AF:

0.910

Gnomad SAS

AF:

0.963

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.988

Gnomad OTH

AF:

0.968

GnomAD2 exomes

AF:

0.972

AC:

244454

AN:

251422

AF XY:

0.974

show subpopulations

Gnomad AFR exome

AF:

0.928

Gnomad AMR exome

AF:

0.961

Gnomad ASJ exome

AF:

0.968

Gnomad EAS exome

AF:

0.912

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.989

Gnomad OTH exome

AF:

0.979

GnomAD4 exome

AF:

0.982

AC:

1434943

AN:

1461430

Hom.:

704758

Cov.:

AF XY:

0.982

AC XY:

713698

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.929

AC:

31098

AN:

33468

American (AMR)

AF:

0.963

AC:

43047

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.968

AC:

25292

AN:

26130

East Asian (EAS)

AF:

0.906

AC:

35969

AN:

39692

South Asian (SAS)

AF:

0.966

AC:

83349

AN:

86242

European-Finnish (FIN)

AF:

0.999

AC:

53355

AN:

53414

Middle Eastern (MID)

AF:

0.979

AC:

5646

AN:

5768

European-Non Finnish (NFE)

AF:

0.988

AC:

1098277

AN:

1111618

Other (OTH)

AF:

0.976

AC:

58910

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1262

2525

3787

5050

6312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21656

43312

64968

86624

108280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.967

AC:

147253

AN:

152274

Hom.:

71261

Cov.:

AF XY:

0.968

AC XY:

72015

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.929

AC:

38586

AN:

41536

American (AMR)

AF:

0.971

AC:

14844

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.969

AC:

3366

AN:

3472

East Asian (EAS)

AF:

0.910

AC:

4708

AN:

5174

South Asian (SAS)

AF:

0.964

AC:

4645

AN:

4820

European-Finnish (FIN)

AF:

0.999

AC:

10607

AN:

10618

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.988

AC:

67252

AN:

68042

Other (OTH)

AF:

0.967

AC:

2042

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

241

483

724

966

1207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.980

Hom.:

98894

Bravo

AF:

0.962

Asia WGS

AF:

0.923

AC:

3211

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant 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: MAF -

Ciliary dyskinesia, primary, 40

Benign:1

Jul 30, 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

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.32

(source)

DANN

Benign

0.25

PhyloP100

0.28

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over