chr14-20369561-C-G

Position:

• chr14-20369561-C-G

Variant summary

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

The NM_007110.5(TEP1):​c.7439G>C​(p.Cys2480Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEP1 NM_007110.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.518

Genes affected

TEP1 (HGNC:11726): (telomerase associated protein 1) This gene product is a component of the ribonucleoprotein complex responsible for telomerase activity which catalyzes the addition of new telomeres on the chromosome ends. The telomerase-associated proteins are conserved from ciliates to humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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	UniProt
TEP1	NM_007110.5	c.7439G>C	p.Cys2480Ser	missense_variant	53/55	ENST00000262715.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEP1	ENST00000262715.10	c.7439G>C	p.Cys2480Ser	missense_variant	53/55	1	NM_007110.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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 18, 2022

The c.7439G>C (p.C2480S) alteration is located in exon 53 (coding exon 52) of the TEP1 gene. This alteration results from a G to C substitution at nucleotide position 7439, causing the cysteine (C) at amino acid position 2480 to be replaced by a serine (S). 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	Pathogenic	0.69
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	0.56	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		0.92	P;P
Vest4		0.47
MutPred		0.52		Gain of disorder (P = 0.0017);.;
MVP		0.66
MPC		0.31
ClinPred		0.88	D
GERP RS		4.0
Varity_R		0.21
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -7

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: chr14-20837720;