rs1713456

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. C1468F) has been classified as Uncertain significance.

• 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
• Publications: 25 publications found

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]

TEP1 Gene-Disease associations (from GenCC):

• cerebral palsy

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007110.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	NM_007110.5	MANE Select	c.4403G>A	p.Cys1468Tyr	missense	Exon 30 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.4079G>A	p.Cys1360Tyr	missense	Exon 28 of 53	NP_001305964.1	G3V5X7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	ENST00000262715.10	TSL:1 MANE Select	c.4403G>A	p.Cys1468Tyr	missense	Exon 30 of 55	ENSP00000262715.5	Q99973-1
	TEP1	ENST00000556935.5	TSL:1	c.4079G>A	p.Cys1360Tyr	missense	Exon 28 of 53	ENSP00000452574.1	G3V5X7
	TEP1	ENST00000555008.5	TSL:1	n.2432G>A		non_coding_transcript_exon	Exon 18 of 43	ENSP00000450541.1	G3V2A4

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

GnomAD2 exomes AF: 0.197 AC: 49396 AN: 250592 AF XY: 0.194

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 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

African (AFR) AF: 0.420 AC: 14045 AN: 33474

American (AMR) AF: 0.177 AC: 7923 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 6307 AN: 26130

East Asian (EAS) AF: 0.100 AC: 3980 AN: 39700

South Asian (SAS) AF: 0.191 AC: 16501 AN: 86252

European-Finnish (FIN) AF: 0.189 AC: 10082 AN: 53318

Middle Eastern (MID) AF: 0.241 AC: 1388 AN: 5768

European-Non Finnish (NFE) AF: 0.180 AC: 200467 AN: 1111964

Other (OTH) AF: 0.194 AC: 11717 AN: 60386

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

African (AFR) AF: 0.407 AC: 16842 AN: 41410

American (AMR) AF: 0.192 AC: 2932 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 831 AN: 3466

East Asian (EAS) AF: 0.101 AC: 523 AN: 5178

South Asian (SAS) AF: 0.201 AC: 970 AN: 4822

European-Finnish (FIN) AF: 0.194 AC: 2054 AN: 10580

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12501 AN: 67984

Other (OTH) AF: 0.235 AC: 495 AN: 2104

Alfa AF: 0.201 Hom.: 11967

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 v4.9

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
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.8	N
PhyloP100		0.37
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	3.6	N
REVEL	Benign	0.096
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	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
Mutation Taster		=295/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1713456; hg19: chr14-20850093; COSMIC: COSV52989026; COSMIC: COSV52989026;