16-58254118-C-T

Position:

• chr16-58254118-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014157.4(CCDC113):​c.349C>T​(p.His117Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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)
• Consequence: CCDC113 NM_014157.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33914745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC113	NM_014157.4	c.349C>T	p.His117Tyr	missense_variant	3/9	ENST00000219299.8	NP_054876.2
CCDC113	NM_001142302.2	c.228+1265C>T		intron_variant			NP_001135774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC113	ENST00000219299.8	c.349C>T	p.His117Tyr	missense_variant	3/9	1	NM_014157.4	ENSP00000219299.4
CCDC113	ENST00000443128.6	c.228+1265C>T		intron_variant		2		ENSP00000402588.2
CCDC113	ENST00000561517.5	n.101+4003C>T		intron_variant		4		ENSP00000454618.1
CCDC113	ENST00000569374.1	c.*22C>T		downstream_gene_variant		4		ENSP00000455923.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 26, 2024

The c.349C>T (p.H117Y) 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 349, causing the histidine (H) at amino acid position 117 to be replaced by a tyrosine (Y). 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	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.087
Sift	Benign	0.055	T;.
Sift4G	Uncertain	0.043	D;D
Polyphen		0.94	P;.
Vest4		0.38
MutPred		0.21		Loss of disorder (P = 0.0315);Loss of disorder (P = 0.0315);
MVP		0.58
MPC		0.33
ClinPred		0.89	D
GERP RS		5.5
Varity_R		0.13
gMVP		0.28

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: chr16-58288022;