19-48303693-C-T

Variant names:

• chr19-48303693-C-T
• rs746835308
• NM_001364171.2:c.945G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001364171.2(ODAD1):​c.945G>A​(p.Met315Ile) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M315V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.30
• Publications: 0 publications found

Genes affected

ODAD1 (HGNC:26560): (outer dynein arm docking complex subunit 1) This gene encodes a coiled-coil domain-containing protein that is a component of the outer dynein arm docking complex in cilia cells. Mutations in this gene may cause primary ciliary dyskinesia 20. [provided by RefSeq, May 2013]

ODAD1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 20

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052354693).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364171.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	NM_001364171.2	MANE Select	c.945G>A	p.Met315Ile	missense	Exon 10 of 16	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.834G>A	p.Met278Ile	missense	Exon 8 of 14	NP_653178.3	Q96M63-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	ENST00000674294.1	MANE Select	c.945G>A	p.Met315Ile	missense	Exon 10 of 16	ENSP00000501363.1	A0A6I8PTZ2
	ODAD1	ENST00000315396.7	TSL:1	c.834G>A	p.Met278Ile	missense	Exon 8 of 14	ENSP00000318429.7	Q96M63-1
	ODAD1	ENST00000859784.1		c.945G>A	p.Met315Ile	missense	Exon 9 of 15	ENSP00000529843.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.0010
DANN	Benign	0.87
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		-4.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.036
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.086	T
Polyphen		0.0040	B
Vest4		0.20
MutPred		0.28		Loss of ubiquitination at K273 (P = 0.0675)
MVP		0.16
MPC		0.22
ClinPred		0.076	T
GERP RS		-6.0
Varity_R		0.14
gMVP		0.39
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs746835308; hg19: chr19-48806950;