14-20408094-A-G

Position:

• chr14-20408094-A-G

Variant summary

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

The NM_007110.5(TEP1):​c.346T>C​(p.Ser116Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,613,824 control chromosomes in the GnomAD database, including 87,221 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S116C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.36 (10842 hom., cov: 31)
  • Exomes 𝑓: 0.32 (76379 hom.)
• Consequence: TEP1 NM_007110.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652

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=8.303092E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEP1	NM_007110.5	c.346T>C	p.Ser116Pro	missense_variant	2/55	ENST00000262715.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEP1	ENST00000262715.10	c.346T>C	p.Ser116Pro	missense_variant	2/55	1	NM_007110.5	P1
TEP1	ENST00000556935.5	c.346T>C	p.Ser116Pro	missense_variant	2/53	1
TEP1	ENST00000555727.5	c.346T>C	p.Ser116Pro	missense_variant, NMD_transcript_variant	2/54	1
TEP1	ENST00000556549.1	c.346T>C	p.Ser116Pro	missense_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55381 AN: 151832 Hom.: 10817 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.362

GnomAD3 exomes AF: 0.331 AC: 83278 AN: 251460 Hom.: 14589 AF XY: 0.329 AC XY: 44741 AN XY: 135902

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.176

Gnomad SAS exome AF: 0.370

Gnomad FIN exome AF: 0.287

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.320 AC: 467312 AN: 1461874 Hom.: 76379 Cov.: 54 AF XY: 0.321 AC XY: 233328 AN XY: 727236

Gnomad4 AFR exome AF: 0.497

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.413

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.378

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.365 AC: 55436 AN: 151950 Hom.: 10842 Cov.: 31 AF XY: 0.362 AC XY: 26872 AN XY: 74252

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.364

Alfa AF: 0.321 Hom.: 20004

Bravo AF: 0.376

TwinsUK AF: 0.309 AC: 1144

ALSPAC AF: 0.316 AC: 1218

ESP6500AA AF: 0.510 AC: 2249

ESP6500EA AF: 0.318 AC: 2731

ExAC AF: 0.334 AC: 40511

Asia WGS AF: 0.305 AC: 1058 AN: 3478

EpiCase AF: 0.312

EpiControl AF: 0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.24
DANN	Benign	0.086
DEOGEN2	Benign	0.038	T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.12	T;T;T
MetaRNN	Benign	0.000083	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.2	N;.;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.1	N;N;N
REVEL	Benign	0.010
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.062
MPC		0.14
ClinPred		0.0013	T
GERP RS		-0.63
Varity_R		0.086
gMVP		0.20

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: rs1760897; hg19: chr14-20876253; COSMIC: COSV52989178; COSMIC: COSV52989178;