16-58254023-C-A

Position:

• chr16-58254023-C-A

Variant summary

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

The NM_014157.4(CCDC113):​c.254C>A​(p.Ser85Tyr) 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: 1.93

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=0.34061724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC113	NM_014157.4	c.254C>A	p.Ser85Tyr	missense_variant	3/9	ENST00000219299.8	NP_054876.2
CCDC113	NM_001142302.2	c.228+1170C>A		intron_variant			NP_001135774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC113	ENST00000219299.8	c.254C>A	p.Ser85Tyr	missense_variant	3/9	1	NM_014157.4	ENSP00000219299.4
CCDC113	ENST00000569374.1	c.119C>A	p.Ser40Tyr	missense_variant	4/4	4		ENSP00000455923.1
CCDC113	ENST00000443128.6	c.228+1170C>A		intron_variant		2		ENSP00000402588.2
CCDC113	ENST00000561517.5	n.101+3908C>A		intron_variant		4		ENSP00000454618.1

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

Nov 14, 2024

The c.254C>A (p.S85Y) alteration is located in exon 3 (coding exon 3) of the CCDC113 gene. This alteration results from a C to A substitution at nucleotide position 254, causing the serine (S) at amino acid position 85 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	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	.;T;.
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.5	.;M;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.7	D;D;.
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D;D;.
Sift4G	Uncertain	0.012	D;D;D
Polyphen		0.98	.;D;.
Vest4		0.28, 0.30
MutPred		0.23		.;Loss of phosphorylation at S85 (P = 0.0311);Loss of phosphorylation at S85 (P = 0.0311);
MVP		0.55
MPC		0.37
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.12
gMVP		0.34

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

Other links and lift over

dbSNP: rs1400547103; hg19: chr16-58287927;