chr17-11598522-C-A

Variant names:

• chr17-11598522-C-A
• rs751934212
• NM_001372.4:c.24C>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001372.4(DNAH9):​c.24C>A​(p.Ala8Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000052 in 1,345,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: DNAH9 NM_001372.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-3.23 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4	c.24C>A	p.Ala8Ala	synonymous_variant	Exon 1 of 69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9	c.24C>A	p.Ala8Ala	synonymous_variant	Exon 1 of 69	1	NM_001372.4	ENSP00000262442.3
DNAH9	ENST00000579406.1	n.51C>A		non_coding_transcript_exon_variant	Exon 1 of 8	1
DNAH9	ENST00000454412.6	c.24C>A	p.Ala8Ala	synonymous_variant	Exon 1 of 68	5		ENSP00000414874.2
DNAH9	ENST00000579828.5	c.24C>A	p.Ala8Ala	synonymous_variant	Exon 1 of 4	2		ENSP00000463782.1

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 147210 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD4 exome AF: 0.00000417 AC: 5 AN: 1198368 Hom.: 0 Cov.: 33 AF XY: 0.00000171 AC XY: 1 AN XY: 584048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000511

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 147210 Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 1 AN XY: 71792

Gnomad4 AFR AF: 0.0000486

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.2
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs751934212; hg19: chr17-11501839;