rs1713456

Variant names:

• chr14-20381934-C-T
• rs1713456
• NM_007110.5:c.4403G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007110.5(TEP1):​c.4403G>A​(p.Cys1468Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,613,728 control chromosomes in the GnomAD database, including 32,302 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.25 (5407 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26895 hom.)
• Consequence: TEP1 NM_007110.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032809973).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEP1	NM_007110.5	c.4403G>A	p.Cys1468Tyr	missense_variant	Exon 30 of 55	ENST00000262715.10	NP_009041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10	c.4403G>A	p.Cys1468Tyr	missense_variant	Exon 30 of 55	1	NM_007110.5	ENSP00000262715.5

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37290 AN: 151912 Hom.: 5396 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.229

GnomAD3 exomes AF: 0.197 AC: 49396 AN: 250592 Hom.: 5500 AF XY: 0.194 AC XY: 26277 AN XY: 135432

Gnomad AFR exome AF: 0.412

Gnomad AMR exome AF: 0.175

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.0991

Gnomad SAS exome AF: 0.195

Gnomad FIN exome AF: 0.193

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.186 AC: 272410 AN: 1461698 Hom.: 26895 Cov.: 35 AF XY: 0.186 AC XY: 135353 AN XY: 727168

Gnomad4 AFR exome AF: 0.420

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.246 AC: 37331 AN: 152030 Hom.: 5407 Cov.: 32 AF XY: 0.243 AC XY: 18051 AN XY: 74342

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.235

Alfa AF: 0.193 Hom.: 7591

Bravo AF: 0.252

TwinsUK AF: 0.170 AC: 631

ALSPAC AF: 0.182 AC: 703

ESP6500AA AF: 0.379 AC: 1672

ESP6500EA AF: 0.184 AC: 1579

ExAC AF: 0.203 AC: 24696

Asia WGS AF: 0.215 AC: 752 AN: 3478

EpiCase AF: 0.183

EpiControl AF: 0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.50
DEOGEN2	Benign	0.062	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.13	T;T
MetaRNN	Benign	0.0033	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.8	N;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	3.6	N;N
REVEL	Benign	0.096
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.11
MPC		0.19
ClinPred		0.0087	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.053
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1713456; hg19: chr14-20850093; COSMIC: COSV52989026; COSMIC: COSV52989026;