Variant 16-58258369-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_014157.4(CCDC113):c.392C>T(p.Ala131Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000319 in 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

CCDC113
NM_014157.4 missense, splice_region

Scores

Splicing: ADA: 0.1072

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

Variant links:

Genes affected

CCDC113 (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]

CCDC113 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	Protein	UniProt
CCDC113	NM_014157.4 linkuse as main transcript	c.392C>T	p.Ala131Val	missense_variant, splice_region_variant	4/9	ENST00000219299.8	NP_054876.2
CCDC113	NM_001142302.2 linkuse as main transcript	c.230C>T	p.Ala77Val	missense_variant, splice_region_variant	3/8		NP_001135774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC113	ENST00000219299.8 linkuse as main transcript	c.392C>T	p.Ala131Val	missense_variant, splice_region_variant	4/9	1	NM_014157.4	ENSP00000219299	P1	Q9H0I3-1
CCDC113	ENST00000443128.6 linkuse as main transcript	c.230C>T	p.Ala77Val	missense_variant, splice_region_variant	3/8	2		ENSP00000402588		Q9H0I3-2
CCDC113	ENST00000561517.5 linkuse as main transcript	c.103C>T	p.Arg35Ter	stop_gained, splice_region_variant, NMD_transcript_variant	2/4	4		ENSP00000454618

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000171

AC:

AN:

251214

Hom.:

AF XY:

0.000206

AC XY:

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000331

AC:

484

AN:

1461298

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

248

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000390

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.000204

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.000208

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000189

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2021

The c.392C>T (p.A131V) alteration is located in exon 4 (coding exon 4) of the CCDC113 gene. This alteration results from a C to T substitution at nucleotide position 392, causing the alanine (A) at amino acid position 131 to be replaced by a valine (V). 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

Pathogenic

0.80

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

.;T;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.42

T;T;T

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.7

.;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.2

D;D;.

REVEL

Benign

0.17

Sift

Uncertain

0.0050

D;D;.

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

0.99

.;D;.

Vest4

0.74

MVP

0.60

MPC

0.38

ClinPred

0.25

GERP RS

4.5

Varity_R

0.49

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.11

dbscSNV1_RF

Benign

0.31

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