14-20378791-C-T

Variant names:

• chr14-20378791-C-T
• rs8022805
• NM_007110.5:c.5315G>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.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. 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. R1772W) has been classified as Uncertain significance.

• 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
• Publications: 13 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]

ACMG classification

Our verdict: Benign. The variant received -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

GnomAD2 exomes AF: 0.0490 AC: 12305 AN: 251234 AF XY: 0.0529

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 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

African (AFR) AF: 0.00812 AC: 272 AN: 33480

American (AMR) AF: 0.0255 AC: 1141 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0747 AC: 1953 AN: 26134

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39700

South Asian (SAS) AF: 0.0831 AC: 7165 AN: 86250

European-Finnish (FIN) AF: 0.0635 AC: 3389 AN: 53404

Middle Eastern (MID) AF: 0.0695 AC: 401 AN: 5768

European-Non Finnish (NFE) AF: 0.0551 AC: 61245 AN: 1111974

Other (OTH) AF: 0.0505 AC: 3051 AN: 60394

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

African (AFR) AF: 0.0102 AC: 425 AN: 41580

American (AMR) AF: 0.0330 AC: 505 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0839 AC: 405 AN: 4828

European-Finnish (FIN) AF: 0.0676 AC: 717 AN: 10608

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0530 AC: 3604 AN: 68020

Other (OTH) AF: 0.0455 AC: 96 AN: 2112

Alfa AF: 0.0492 Hom.: 632

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;.
PhyloP100		0.55
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
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8022805; hg19: chr14-20846950;