14-20378791-C-T

Variant names:

• chr14-20378791-C-T
• rs8022805
• NM_007110.5:c.5315G>A

Variant summary

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

The NM_007110.5(TEP1):​c.5315G>A​(p.Arg1772Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 1,614,140 control chromosomes in the GnomAD database, including 2,556 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 0.040 (166 hom., cov: 33)
  • Exomes 𝑓: 0.054 (2390 hom.)
• Consequence: TEP1 NM_007110.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547

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=0.0037632883).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEP1	NM_007110.5	c.5315G>A	p.Arg1772Gln	missense_variant	Exon 37 of 55	ENST00000262715.10	NP_009041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10	c.5315G>A	p.Arg1772Gln	missense_variant	Exon 37 of 55	1	NM_007110.5	ENSP00000262715.5

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 6052 AN: 152194 Hom.: 166 Cov.: 33

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.0676

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.0459

GnomAD3 exomes AF: 0.0490 AC: 12305 AN: 251234 Hom.: 433 AF XY: 0.0529 AC XY: 7176 AN XY: 135774

Gnomad AFR exome AF: 0.00868

Gnomad AMR exome AF: 0.0239

Gnomad ASJ exome AF: 0.0750

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.0849

Gnomad FIN exome AF: 0.0671

Gnomad NFE exome AF: 0.0547

Gnomad OTH exome AF: 0.0515

GnomAD4 exome AF: 0.0538 AC: 78628 AN: 1461828 Hom.: 2390 Cov.: 33 AF XY: 0.0551 AC XY: 40073 AN XY: 727220

Gnomad4 AFR exome AF: 0.00812

Gnomad4 AMR exome AF: 0.0255

Gnomad4 ASJ exome AF: 0.0747

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.0831

Gnomad4 FIN exome AF: 0.0635

Gnomad4 NFE exome AF: 0.0551

Gnomad4 OTH exome AF: 0.0505

GnomAD4 genome AF: 0.0397 AC: 6049 AN: 152312 Hom.: 166 Cov.: 33 AF XY: 0.0408 AC XY: 3042 AN XY: 74472

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.0330

Gnomad4 ASJ AF: 0.0717

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0839

Gnomad4 FIN AF: 0.0676

Gnomad4 NFE AF: 0.0530

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0487 Hom.: 286

Bravo AF: 0.0348

TwinsUK AF: 0.0580 AC: 215

ALSPAC AF: 0.0514 AC: 198

ESP6500AA AF: 0.0109 AC: 48

ESP6500EA AF: 0.0578 AC: 497

ExAC AF: 0.0494 AC: 6001

Asia WGS AF: 0.0280 AC: 97 AN: 3478

EpiCase AF: 0.0556

EpiControl AF: 0.0564

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.72	T;T
MetaRNN	Benign	0.0038	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.27
Sift	Benign	0.16	T;T
Sift4G	Uncertain	0.017	D;D
Polyphen		1.0	D;D
Vest4		0.12
MPC		0.22
ClinPred		0.011	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.20

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

LitVar

Other links and lift over

dbSNP: rs8022805; hg19: chr14-20846950;