rs546138389

Positions:

chr19-11423882-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145045.5(ODAD3):c.1111A>G(p.Thr371Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,607,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ODAD3
NM_145045.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.0230

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=0.109788954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ODAD3	NM_145045.5 linkuse as main transcript	c.1111A>G	p.Thr371Ala	missense_variant	8/13	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302453.1 linkuse as main transcript	c.949A>G	p.Thr317Ala	missense_variant	8/13		NP_001289382.1
ODAD3	NM_001302454.2 linkuse as main transcript	c.931A>G	p.Thr311Ala	missense_variant	6/11		NP_001289383.1
ODAD3	XM_017026241.2 linkuse as main transcript	c.*5A>G		3_prime_UTR_variant	8/9		XP_016881730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9 linkuse as main transcript	c.1111A>G	p.Thr371Ala	missense_variant	8/13	1	NM_145045.5	ENSP00000348757	P2	A5D8V7-1
ODAD3	ENST00000591179.5 linkuse as main transcript	c.931A>G	p.Thr311Ala	missense_variant	6/11	1		ENSP00000466800	A2
ODAD3	ENST00000586836.5 linkuse as main transcript	c.538A>G	p.Thr180Ala	missense_variant	8/13	2		ENSP00000467429	A2
ODAD3	ENST00000591345.5 linkuse as main transcript	c.*1030A>G		3_prime_UTR_variant, NMD_transcript_variant	9/14	5		ENSP00000467313

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000284

AC:

AN:

246644

Hom.:

AF XY:

0.0000373

AC XY:

AN XY:

134138

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:

0.0000625

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1456572

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

724356

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:

0.0000288

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73718

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000590

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000786

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.00000825

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.1111A>G (p.T371A) alteration is located in exon 8 (coding exon 8) of the CCDC151 gene. This alteration results from a A to G substitution at nucleotide position 1111, causing the threonine (T) at amino acid position 371 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Primary ciliary dyskinesia 30

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 11, 2021

This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 371 of the CCDC151 protein (p.Thr371Ala). This variant is present in population databases (rs546138389, gnomAD 0.008%). 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: 582033). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.43

CADD

Benign

4.1

DANN

Benign

0.46

DEOGEN2

Benign

0.0031

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.077

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.2

N;.;.

REVEL

Benign

0.16

Sift

Benign

0.33

T;.;.

Sift4G

Benign

0.85

T;T;T

Polyphen

0.016

B;.;.

Vest4

0.40

MVP

0.26

MPC

0.47

ClinPred

0.031

GERP RS

-0.92

Varity_R

0.045

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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