rs200305902

Positions:

chr19-11426690-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting

The NM_145045.5(ODAD3):c.707A>G(p.Tyr236Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

ODAD3
NM_145045.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 2.86

Variant links:

Genes affected

ODAD3 (HGNC:28303): (outer dynein arm docking complex subunit 3) This gene encodes a protein containing coiled-coil domains. The encoded protein functions in outer dynein arm assembly and is required for motile cilia function. Mutations in this gene result in primary ciliary dyskinesia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

ODAD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2861225).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000269 (41/152174) while in subpopulation NFE AF= 0.000485 (33/68014). AF 95% confidence interval is 0.000354. There are 0 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ODAD3	NM_145045.5 linkuse as main transcript	c.707A>G	p.Tyr236Cys	missense_variant	5/13	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302453.1 linkuse as main transcript	c.545A>G	p.Tyr182Cys	missense_variant	5/13		NP_001289382.1
ODAD3	XM_017026241.2 linkuse as main transcript	c.707A>G	p.Tyr236Cys	missense_variant	5/9		XP_016881730.1
ODAD3	NM_001302454.2 linkuse as main transcript	c.535-119A>G		intron_variant			NP_001289383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9 linkuse as main transcript	c.707A>G	p.Tyr236Cys	missense_variant	5/13	1	NM_145045.5	ENSP00000348757	P2	A5D8V7-1
ODAD3	ENST00000591179.5 linkuse as main transcript	c.535-119A>G		intron_variant		1		ENSP00000466800	A2
ODAD3	ENST00000586836.5 linkuse as main transcript	c.134A>G	p.Tyr45Cys	missense_variant	5/13	2		ENSP00000467429	A2
ODAD3	ENST00000591345.5 linkuse as main transcript	c.*626A>G		3_prime_UTR_variant, NMD_transcript_variant	6/14	5		ENSP00000467313

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000209

AC:

AN:

248348

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

134768

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000658

Gnomad NFE exome

AF:

0.000329

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000165

AC:

241

AN:

1461654

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

133

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000487

Gnomad4 NFE exome

AF:

0.000187

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000269

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000344

Hom.:

Bravo

AF:

0.000166

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 30

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 236 of the CCDC151 protein (p.Tyr236Cys). This variant is present in population databases (rs200305902, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with CCDC151-related conditions. ClinVar contains an entry for this variant (Variation ID: 477986). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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. -
Uncertain significance, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Feb 15, 2022	- -

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2021

The c.707A>G (p.Y236C) alteration is located in exon 5 (coding exon 5) of the CCDC151 gene. This alteration results from a A to G substitution at nucleotide position 707, causing the tyrosine (Y) at amino acid position 236 to be replaced by a cysteine (C). 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

0.21

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

T;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

T;T

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.29

T;T

MetaSVM

Uncertain

0.33

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

0.96

D;D;D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.4

D;.

REVEL

Uncertain

0.61

Sift

Benign

0.11

T;.

Sift4G

Benign

0.17

T;T

Polyphen

1.0

D;.

Vest4

0.46

MVP

0.87

MPC

0.59

ClinPred

0.30

GERP RS

4.8

Varity_R

0.24

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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