3-123915430-G-T

Position:

• chr3-123915430-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366335.1(CCDC14):​c.2067C>A​(p.Asn689Lys) 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC14 NM_001366335.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.426

Genes affected

CCDC14 (HGNC:25766): (coiled-coil domain containing 14) Involved in protein localization to centrosome. Located in centriolar satellite. [provided by Alliance of Genome Resources, Apr 2022]

CCDC14 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.083987445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC14	NM_001366335.1	c.2067C>A	p.Asn689Lys	missense_variant	13/13	ENST00000409697.8	NP_001353264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC14	ENST00000409697.8	c.2067C>A	p.Asn689Lys	missense_variant	13/13	2	NM_001366335.1	ENSP00000386866.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Mar 25, 2024

The c.2088C>A (p.N696K) alteration is located in exon 12 (coding exon 12) of the CCDC14 gene. This alteration results from a C to A substitution at nucleotide position 2088, causing the asparagine (N) at amino acid position 696 to be replaced by a lysine (K). 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
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.027	.;.;.;T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.70	T;.;T;T;.;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.084	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.6	.;N;N;.;N;.
REVEL	Benign	0.062
Sift	Benign	0.25	.;T;T;.;T;.
Sift4G	Benign	0.10	T;T;T;T;T;T
Polyphen		0.0020	B;.;.;.;B;.
Vest4		0.060
MVP		0.17
MPC		0.35
ClinPred		0.090	T
GERP RS		-0.61
gMVP		0.094

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: chr3-123634277;