dbSNP rs555429163: DNAH9:p.Leu3Val (chr17-11598505-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001372.4(DNAH9):c.7C>G(p.Leu3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAH9
NM_001372.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.00

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034835577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH9	NM_001372.4 link	c.7C>G	p.Leu3Val	missense_variant	Exon 1 of 69	ENST00000262442.9	NP_001363.2	Q9NYC9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH9	ENST00000262442.9 link	c.7C>G	p.Leu3Val	missense_variant	Exon 1 of 69	1	NM_001372.4	ENSP00000262442.3	Q9NYC9-1
DNAH9	ENST00000579406.1 link	n.34C>G		non_coding_transcript_exon_variant	Exon 1 of 8	1
DNAH9	ENST00000454412.6 link	c.7C>G	p.Leu3Val	missense_variant	Exon 1 of 68	5		ENSP00000414874.2	E7EP17
DNAH9	ENST00000579828.5 link	c.7C>G	p.Leu3Val	missense_variant	Exon 1 of 4	2		ENSP00000463782.1	J3QQK8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1224520

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

595742

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Sep 06, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3 of the DNAH9 protein (p.Leu3Val). This variant is not present in population databases (gnomAD no frequency). 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.42

DANN

Benign

0.29

DEOGEN2

Benign

0.0070

T;.;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.38

T;T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.040

N;.;N

REVEL

Benign

0.0080

Sift

Benign

0.59

T;.;T

Sift4G

Benign

0.41

.;T;.

Polyphen

0.0030

B;.;B

Vest4

0.053

MutPred

0.11

Gain of MoRF binding (P = 0.1844);Gain of MoRF binding (P = 0.1844);Gain of MoRF binding (P = 0.1844);

MVP

0.092

MPC

0.088

ClinPred

0.026

GERP RS

-2.7

Varity_R

0.025

gMVP

0.19

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