16-58259893-C-G

Position:

• chr16-58259893-C-G

Variant summary

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

The NM_014157.4(CCDC113):​c.586C>G​(p.Leu196Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC113 NM_014157.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.20

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]

ACMG classification

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	c.586C>G	p.Leu196Val	missense_variant	5/9	ENST00000219299.8	NP_054876.2
CCDC113	NM_001142302.2	c.424C>G	p.Leu142Val	missense_variant	4/8		NP_001135774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC113	ENST00000219299.8	c.586C>G	p.Leu196Val	missense_variant	5/9	1	NM_014157.4	ENSP00000219299	P1
CCDC113	ENST00000443128.6	c.424C>G	p.Leu142Val	missense_variant	4/8	2		ENSP00000402588
CCDC113	ENST00000561517.5	c.*120C>G		3_prime_UTR_variant, NMD_transcript_variant	3/4	4		ENSP00000454618

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.586C>G (p.L196V) alteration is located in exon 5 (coding exon 5) of the CCDC113 gene. This alteration results from a C to G substitution at nucleotide position 586, causing the leucine (L) at amino acid position 196 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	Benign	0.20
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	D;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Pathogenic	3.2	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	.;D
Vest4		0.56
MutPred		0.49		.;Gain of methylation at K197 (P = 0.0351);
MVP		0.55
MPC		0.43
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.50
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-58293797;