rs117483481

Variant names:

• chr17-11854038-G-A
• rs117483481
• NM_001372.4:c.9543G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001372.4(DNAH9):​c.9543G>A​(p.Pro3181Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,614,032 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0042 (45 hom.)
• Consequence: DNAH9 NM_001372.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -5.31
• Publications: 3 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: 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-11854038-G-A is Benign according to our data. Variant chr17-11854038-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 402781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.31 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00368 (560/152192) while in subpopulation EAS AF = 0.0321 (166/5170). AF 95% confidence interval is 0.0281. There are 3 homozygotes in GnomAd4. There are 263 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

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.9543G>A	p.Pro3181Pro	synonymous	Exon 50 of 69	NP_001363.2	Q9NYC9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH9	ENST00000262442.9	TSL:1 MANE Select	c.9543G>A	p.Pro3181Pro	synonymous	Exon 50 of 69	ENSP00000262442.3	Q9NYC9-1
	DNAH9	ENST00000454412.6	TSL:5	c.9543G>A	p.Pro3181Pro	synonymous	Exon 50 of 68	ENSP00000414874.2	E7EP17
	DNAH9	ENST00000578834.1	TSL:4	n.90G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 561 AN: 152074 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0320

Gnomad SAS AF: 0.00644

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00362

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00589 AC: 1479 AN: 251242 AF XY: 0.00585

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.0370

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00356

Gnomad OTH exome AF: 0.00473

GnomAD4 exome AF: 0.00420 AC: 6139 AN: 1461840 Hom.: 45 Cov.: 30 AF XY: 0.00427 AC XY: 3103 AN XY: 727220

African (AFR) AF: 0.000896 AC: 30 AN: 33480

American (AMR) AF: 0.00174 AC: 78 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0108 AC: 282 AN: 26134

East Asian (EAS) AF: 0.0225 AC: 892 AN: 39698

South Asian (SAS) AF: 0.00589 AC: 508 AN: 86256

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53404

Middle Eastern (MID) AF: 0.0107 AC: 62 AN: 5768

European-Non Finnish (NFE) AF: 0.00352 AC: 3911 AN: 1111988

Other (OTH) AF: 0.00604 AC: 365 AN: 60390

GnomAD4 genome AF: 0.00368 AC: 560 AN: 152192 Hom.: 3 Cov.: 31 AF XY: 0.00353 AC XY: 263 AN XY: 74404

African (AFR) AF: 0.00101 AC: 42 AN: 41524

American (AMR) AF: 0.00223 AC: 34 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3470

East Asian (EAS) AF: 0.0321 AC: 166 AN: 5170

South Asian (SAS) AF: 0.00624 AC: 30 AN: 4806

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00362 AC: 246 AN: 68014

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00367 Hom.: 3

Bravo AF: 0.00365

Asia WGS AF: 0.00837 AC: 29 AN: 3478

EpiCase AF: 0.00376

EpiControl AF: 0.00462

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Ciliary dyskinesia, primary, 40 (1)
-	-	1	DNAH9-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.81
PhyloP100		-5.3
PromoterAI		-0.066	Neutral
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs117483481; hg19: chr17-11757355; COSMIC: COSV52361175; COSMIC: COSV52361175;