Genetic Variant NM_001372.4:c.24C>G (chr17-11598522-C-G) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001372.4(DNAH9):c.24C>G(p.Ala8Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000669 in 1,345,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A8A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000067 ( 0 hom. )

Consequence

DNAH9
NM_001372.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.23

Publications

0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 17-11598522-C-G is Benign according to our data. Variant chr17-11598522-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1961482.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.23 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	NM_001372.4	MANE Select	c.24C>G	p.Ala8Ala	synonymous	Exon 1 of 69	NP_001363.2	Q9NYC9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.24C>G	p.Ala8Ala	synonymous	Exon 1 of 69	ENSP00000262442.3	Q9NYC9-1
DNAH9	ENST00000579406.1	TSL:1	n.51C>G		non_coding_transcript_exon	Exon 1 of 8
DNAH9	ENST00000454412.6	TSL:5	c.24C>G	p.Ala8Ala	synonymous	Exon 1 of 68	ENSP00000414874.2	E7EP17

Frequencies

GnomAD3 genomes

AF:

0.00000679

AC:

AN:

147210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

16724

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000668

AC:

AN:

1198368

Hom.:

Cov.:

AF XY:

0.00000514

AC XY:

AN XY:

584048

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24320

American (AMR)

AF:

0.00

AC:

AN:

13552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17904

East Asian (EAS)

AF:

0.000181

AC:

AN:

27690

South Asian (SAS)

AF:

0.0000537

AC:

AN:

55910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3560

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

978654

Other (OTH)

AF:

0.00

AC:

AN:

49596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000679

AC:

AN:

147324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71916

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41244

American (AMR)

AF:

0.00

AC:

AN:

14776

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3416

East Asian (EAS)

AF:

0.000195

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9772

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65190

Other (OTH)

AF:

0.00

AC:

AN:

2040

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.0

(source)

DANN

Benign

0.66

PhyloP100

-3.2

PromoterAI

-0.038

Neutral

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over