Variant 17-41936532-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031421.5(ODAD4):c.457G>A(p.Glu153Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,459,842 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ODAD4
NM_031421.5 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.76

Variant links:

Genes affected

ODAD4 (HGNC:25280): (outer dynein arm docking complex subunit 4) This gene encodes a tetratricopeptide repeat domain-containing protein that localizes to ciliary axonmenes and plays a role in the docking of the outer dynein arm to cilia. Mutations in this gene cause severely reduced ciliary motility and the disorder CILD35 (ciliary dyskinesia,primary, 35). Primary ciliary dyskinesia is often associated with recurrent respiratory infections, immotile spermatozoa, and situs inversus; an inversion in left-right body symmetry. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2017]

ODAD4 links:

ODAD4 (HGNC:):

ODAD4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD4	NM_031421.5 linkuse as main transcript	c.457G>A	p.Glu153Lys	missense_variant, splice_region_variant	4/12	ENST00000377540.6	NP_113609.1	Q96NG3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD4	ENST00000377540.6 linkuse as main transcript	c.457G>A	p.Glu153Lys	missense_variant, splice_region_variant	4/12	1	NM_031421.5	ENSP00000478589.1		Q96NG3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249086

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135136

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1459842

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726286

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2021

The c.457G>A (p.E153K) alteration is located in exon 4 (coding exon 4) of the TTC25 gene. This alteration results from a G to A substitution at nucleotide position 457, causing the glutamic acid (E) at amino acid position 153 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Pathogenic

0.57

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-0.43

PrimateAI

Uncertain

0.55

REVEL

Uncertain

0.50

Sift4G

Uncertain

0.043

Polyphen

0.98

Vest4

0.84

MutPred

0.45

Gain of MoRF binding (P = 0.0012);

MVP

0.34

ClinPred

0.96

GERP RS

6.0

Varity_R

0.75

gMVP

0.47

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