Variant 16-58254014-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014157.4(CCDC113):c.245G>A(p.Arg82Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CCDC113
NM_014157.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.197

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023475796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC113	NM_014157.4 linkuse as main transcript	c.245G>A	p.Arg82Lys	missense_variant	3/9	ENST00000219299.8	NP_054876.2	Q9H0I3-1
CCDC113	NM_001142302.2 linkuse as main transcript	c.228+1161G>A		intron_variant			NP_001135774.1	Q9H0I3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC113	ENST00000219299.8 linkuse as main transcript	c.245G>A	p.Arg82Lys	missense_variant	3/9	1	NM_014157.4	ENSP00000219299.4	Q9H0I3-1
CCDC113	ENST00000569374.1 linkuse as main transcript	c.110G>A	p.Arg37Lys	missense_variant	4/4	4		ENSP00000455923.1	H3BQS9
CCDC113	ENST00000443128.6 linkuse as main transcript	c.228+1161G>A		intron_variant		2		ENSP00000402588.2	Q9H0I3-2
CCDC113	ENST00000561517.5 linkuse as main transcript	n.101+3899G>A		intron_variant		4		ENSP00000454618.1	H3BMZ8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727242

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:

0.0000153

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.15

DANN

Benign

0.54

DEOGEN2

Benign

0.010

.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.53

T;T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.023

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.060

.;N;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.080

N;N;.

REVEL

Benign

0.023

Sift

Benign

0.93

T;T;.

Sift4G

Benign

0.56

T;T;T

Polyphen

0.0030

.;B;.

Vest4

0.090, 0.10

MutPred

0.22

.;Gain of methylation at R82 (P = 0.1049);Gain of methylation at R82 (P = 0.1049);

MVP

0.17

MPC

0.073

ClinPred

0.032

GERP RS

-1.1

Varity_R

0.036

gMVP

0.17

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