Variant chr17-11598501-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_001372.4(DNAH9):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,204,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

DNAH9
NM_001372.4 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

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 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH9	NM_001372.4 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/69	ENST00000262442.9	NP_001363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH9	ENST00000262442.9 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/69	1	NM_001372.4	ENSP00000262442	P1	Q9NYC9-1
DNAH9	ENST00000579406.1 linkuse as main transcript	n.30G>A		non_coding_transcript_exon_variant	1/8	1
DNAH9	ENST00000454412.6 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/68	5		ENSP00000414874
DNAH9	ENST00000579828.5 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/4	2		ENSP00000463782

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000498

AC:

AN:

1204918

Hom.:

Cov.:

AF XY:

0.00000513

AC XY:

AN XY:

585116

show subpopulations

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:

0.00000604

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 17, 2021

This sequence change affects the initiator methionine of the DNAH9 mRNA. The next in-frame methionine is located at codon 34. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with DNAH9-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

0.0060

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0063

T;.;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D

PROVEAN

Benign

-0.54

N;.;N

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;.;D

Sift4G

Pathogenic

0.0

.;D;.

Polyphen

0.039

B;.;P

Vest4

0.60

MutPred

0.94

Gain of catalytic residue at M1 (P = 0.0516);Gain of catalytic residue at M1 (P = 0.0516);Gain of catalytic residue at M1 (P = 0.0516);

MVP

0.40

ClinPred

0.36

GERP RS

3.6

Varity_R

0.87

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over