17-41935333-C-A

Variant names:

• chr17-41935333-C-A
• NM_031421.5:c.231C>A

Variant summary

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

The NM_031421.5(ODAD4):​c.231C>A​(p.Asp77Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ODAD4 NM_031421.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.958

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]

ACMG classification

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 rank	MANE	Protein	UniProt
ODAD4	NM_031421.5	c.231C>A	p.Asp77Glu	missense_variant	Exon 2 of 12	ENST00000377540.6	NP_113609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD4	ENST00000377540.6	c.231C>A	p.Asp77Glu	missense_variant	Exon 2 of 12	1	NM_031421.5	ENSP00000478589.1
ODAD4	ENST00000585530.1	n.36C>A		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000479460.1
ODAD4	ENST00000591658.5	n.231C>A		non_coding_transcript_exon_variant	Exon 2 of 10	5		ENSP00000477931.1
ODAD4	ENST00000593239.5	n.231C>A		non_coding_transcript_exon_variant	Exon 2 of 6	3		ENSP00000484975.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.231C>A (p.D77E) alteration is located in exon 2 (coding exon 2) of the TTC25 gene. This alteration results from a C to A substitution at nucleotide position 231, causing the aspartic acid (D) at amino acid position 77 to be replaced by a glutamic acid (E). 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	Uncertain	0.41
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.65	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.61	T
PrimateAI	Uncertain	0.61	T
REVEL	Benign	0.17
Sift4G	Benign	0.076	T
Polyphen		0.92	P
Vest4		0.57
MutPred		0.52		Gain of disorder (P = 0.1223);
MVP		0.18
ClinPred		0.97	D
GERP RS		2.8
Varity_R		0.23
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-40091586;