3-123915607-T-A

Position:

• chr3-123915607-T-A

Variant summary

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

The NM_001366335.1(CCDC14):​c.1890A>T​(p.Gln630His) 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. 12/18 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: 0.0600

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=0.17980525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC14	NM_001366335.1	c.1890A>T	p.Gln630His	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.1890A>T	p.Gln630His	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 02, 2023

The c.1911A>T (p.Q637H) alteration is located in exon 12 (coding exon 12) of the CCDC14 gene. This alteration results from a A to T substitution at nucleotide position 1911, causing the glutamine (Q) at amino acid position 637 to be replaced by a histidine (H). 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	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;.;.;T;.;T
Eigen	Benign	-0.097
Eigen_PC	Benign	-0.095
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.78	T;.;T;T;.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.54	D;D;D;D;N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.4	.;N;N;.;D;.
REVEL	Benign	0.043
Sift	Benign	0.082	.;T;T;.;T;.
Sift4G	Benign	0.072	T;T;T;T;T;T
Polyphen		0.87	P;.;.;.;P;.
Vest4		0.36
MVP		0.60
MPC		0.33
ClinPred		0.84	D
GERP RS		0.26
gMVP		0.57

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: chr3-123634454;