NM_001372.4:c.3369T>C

Variant names:

• chr17-11679772-T-C
• rs8071438
• NM_001372.4:c.3369T>C
• DNAH9 p.Asp1123Asp

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -17 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_StrongBP6_StrongBP7

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 cumulative frequency of 0.98 (AC=1,582,196) in the gnomAD database across 1,613,704 control chromosomes, including 776,019 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.986. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71261 hom., cov: 32)
  • Exomes 𝑓: 0.98 (704758 hom.)
• Consequence: DNAH9 NM_001372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.277
• Publications: 16 publications found

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: ClinGen, G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -17 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BP6Reputable source reports benign		ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).
	BP7Synonymous variant, no splicing impact		Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.9864 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	DNAH9 NM_001372.4	MANE Select	c.3369T>C p.Asp1123Asp	synonymous	Exon 18 of 69	Prot: NP_001363.2 UniProt:

DNAH9 NM_001372.4

MANE Select

HGVSc / HGVSpc.3369T>Cp.Asp1123Asp

Exon rankExon 18 of 69

synonymous

Prot: NP_001363.2UniProt: Q9NYC9-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	DNAH9 ENST00000262442.9	TSL:1MANE Select	c.3369T>C p.Asp1123Asp	synonymous	Exon 18 of 69	Prot: ENSP00000262442.3 UniProt:
	DNAH9 ENST00000454412.6	TSL:5	c.3369T>C p.Asp1123Asp	synonymous	Exon 18 of 68	Prot: ENSP00000414874.2 UniProt:

DNAH9 ENST00000262442.9

TSL:1MANE Select

HGVSc / HGVSpc.3369T>Cp.Asp1123Asp

Exon rankExon 18 of 69

synonymous

Prot: ENSP00000262442.3UniProt: Q9NYC9-1

DNAH9 ENST00000454412.6

TSL:5

HGVSc / HGVSpc.3369T>Cp.Asp1123Asp

Exon rankExon 18 of 68

synonymous

Prot: ENSP00000414874.2UniProt: E7EP17

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.967	AC:147142	Hom:71210	AN:152156	Cov:32
GnomAD2 exomes	AF: 0.972	AC:244454	Hom:	AN:251422	Cov:
GnomAD4 exome	AF: 0.982	AC:1434943	Hom:704758	AN:1461430	Cov:40
GnomAD4 genome	AF: 0.967	AC:147253	Hom:71261	AN:152274	Cov:32
TOPMed (Bravo)	AF: 0.962	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.978	AC:221908	Hom:108567	AN:226866	Cov:
Local & regional cohorts 11 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.962	AC:2253	Hom:1090	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.910	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 1.00	AC:300	Hom:	AN:300	Cov:
ESP6500 (Exome Variant Server)	AF: 0.968	AC:12594	Hom:	AN:13006	Cov:
GenomeAsia100K	AF: 0.923	AC:3211	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.924	AC:6683	Hom:	AN:7232	Cov:
Qatari Genome	AF: 0.984	AC:1978	Hom:	AN:2010	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.899	AC:110431	Hom:49683	AN:122806	Cov:
Turkish Variome	AF: 0.972	AC:6538	Hom:3183	AN:6724	Cov:
UK10K	AF: 0.990	AC:7485	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.910	AC:8156	Hom:3719	AN:8960	Cov:

Showing 17 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.994 *	11043	11112	0.994 *	17503	17616
BipEx(Bipolar disorder (including schizoaffective))	0.991	28159	28420	0.990	28549	28844
Epi25(Epilepsy)	0.976	40946	41958	0.978	65439	66888
SCHEMA(Schizophrenia)	0.892	158070	177146	0.893	268008	300016

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Ciliary dyskinesia, primary, 40 (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.84
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.32
DANN	Benign	0.25
GPN-Star LLR	N/A	2.2
GPN-Star score	N/A	-2.0
Mutation Taster	N/A	99/1	polymorphism (auto)
PhyloP100	Benign	0.28

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs8071438;

hg19: chr17-11583089;

COSMIC: COSV52334757;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar