Genetic Variant CFAP263:p.Arg124Cys (chr16-58254139-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_014157.4(CFAP263):c.370C>T(p.Arg124Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R124H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CFAP263
NM_014157.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.786

Variant links:

Genes affected

CFAP263 (HGNC:25002): (cilia and flagella associated protein 263) Involved in cilium assembly. Located in centriolar satellite and ciliary basal body. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

CFAP263 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 rank	MANE	Protein	UniProt
CFAP263	NM_014157.4 link	c.370C>T	p.Arg124Cys	missense_variant	Exon 3 of 9	ENST00000219299.8	NP_054876.2	Q9H0I3-1
CFAP263	NM_001142302.2 link	c.228+1286C>T		intron_variant	Intron 2 of 7		NP_001135774.1	Q9H0I3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC113	ENST00000219299.8 link	c.370C>T	p.Arg124Cys	missense_variant	Exon 3 of 9	1	NM_014157.4	ENSP00000219299.4	Q9H0I3-1
CCDC113	ENST00000443128.6 link	c.228+1286C>T		intron_variant	Intron 2 of 7	2		ENSP00000402588.2	Q9H0I3-2
CCDC113	ENST00000561517.5 link	n.101+4024C>T		intron_variant	Intron 1 of 3	4		ENSP00000454618.1	H3BMZ8
CCDC113	ENST00000569374.1 link	c.*43C>T		downstream_gene_variant		4		ENSP00000455923.1	H3BQS9

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251460

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135906

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000126

AC:

184

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000158

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000131

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.000169

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:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 20, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.370C>T (p.R124C) alteration is located in exon 3 (coding exon 3) of the CCDC113 gene. This alteration results from a C to T substitution at nucleotide position 370, causing the arginine (R) at amino acid position 124 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

T;.

Eigen

Benign

0.12

Eigen_PC

Benign

-0.016

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.7

D;.

REVEL

Benign

0.16

Sift

Uncertain

0.0010

D;.

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.59

MutPred

0.25

Loss of disorder (P = 0.0324);Loss of disorder (P = 0.0324);

MVP

0.54

MPC

0.47

ClinPred

0.78

GERP RS

4.6

Varity_R

0.30

gMVP

0.50

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

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