Variant 17-44901080-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_213607.3(CCDC103):c.82C>T(p.Arg28Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000374 in 1,604,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

CCDC103
NM_213607.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.648

Variant links:

Genes affected

CCDC103 (HGNC:32700): (coiled-coil domain containing 103) Enables protein homodimerization activity. Involved in axonemal dynein complex assembly; cilium movement; and determination of left/right symmetry. Predicted to be located in axoneme. Predicted to be part of outer dynein arm. Implicated in primary ciliary dyskinesia 17. [provided by Alliance of Genome Resources, Apr 2022]

CCDC103 links:

Genome browser will be placed here

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	UniProt
CCDC103	NM_213607.3 linkuse as main transcript	c.82C>T	p.Arg28Trp	missense_variant	2/4	ENST00000417826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC103	ENST00000417826.3 linkuse as main transcript	c.82C>T	p.Arg28Trp	missense_variant	2/4	1	NM_213607.3	P1	Q8IW40-1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000498

AC:

AN:

240844

Hom.:

AF XY:

0.0000536

AC XY:

AN XY:

130712

show subpopulations

Gnomad AFR exome

AF:

0.000440

Gnomad AMR exome

AF:

0.0000324

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:

0.0000180

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.0000289

AC:

AN:

1451868

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

722536

show subpopulations

Gnomad4 AFR exome

AF:

0.000183

Gnomad4 AMR exome

AF:

0.000146

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000834

GnomAD4 genome

AF:

0.000118

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.000238

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Aug 08, 2022

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 28 of the CCDC103 protein (p.Arg28Trp). This variant is present in population databases (rs144226204, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with CCDC103-related conditions. ClinVar contains an entry for this variant (Variation ID: 242266). 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 disruptive. 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

0.21

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.26

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.069

FATHMM_MKL

Benign

0.15

LIST_S2

Uncertain

0.95

D;.;D;D;.;D

M_CAP

Benign

0.074

MetaRNN

Uncertain

0.66

D;D;D;D;D;D

MetaSVM

Uncertain

0.37

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.46

Sift4G

Uncertain

0.0040

D;D;D;D;D;D

Polyphen

1.0

.;D;.;.;D;.

Vest4

0.72, 0.77, 0.71

MVP

0.82

MPC

0.69

ClinPred

0.99

GERP RS

0.65

Varity_R

0.72

gMVP

0.62

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