14-105498932-C-A

Position:

• chr14-105498932-C-A

Variant summary

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

The NM_001367178.1(TEDC1):​c.1474C>A​(p.Pro492Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: TEDC1 NM_001367178.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.779

Genes affected

TEDC1 (HGNC:20127): (tubulin epsilon and delta complex 1) Predicted to be involved in positive regulation of smoothened signaling pathway. Predicted to be located in centriole and cilium. [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
TEDC1	NM_001367178.1	c.1474C>A	p.Pro492Thr	missense_variant	9/9	ENST00000392523.9	NP_001354107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEDC1	ENST00000392523.9	c.1474C>A	p.Pro492Thr	missense_variant	9/9	1	NM_001367178.1	ENSP00000376308

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

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

Aug 02, 2021

The c.1267C>A (p.P423T) alteration is located in exon 8 (coding exon 8) of the C14orf80 gene. This alteration results from a C to A substitution at nucleotide position 1267, causing the proline (P) at amino acid position 423 to be replaced by a threonine (T). 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	0.25
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;.;.;T;.;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.83	T;T;T;T;T;T;.
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PROVEAN	Pathogenic	-5.9	D;D;D;D;D;.;D
REVEL	Benign	0.096
Sift	Uncertain	0.0040	D;D;D;D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		1.0	D;.;.;D;D;.;.
Vest4		0.55
MutPred		0.56		.;.;.;Loss of disorder (P = 0.0163);.;.;.;
MVP		0.39
MPC		0.12
ClinPred		0.77	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.22
gMVP		0.78

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: chr14-105965269;