14-20376224-C-T

Position:

• chr14-20376224-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007110.5(TEP1):​c.6129G>A​(p.Thr2043Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0611 in 1,614,100 control chromosomes in the GnomAD database, including 3,336 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.046 (227 hom., cov: 32)
  • Exomes 𝑓: 0.063 (3109 hom.)
• Consequence: TEP1 NM_007110.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.39

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-4.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEP1	NM_007110.5	c.6129G>A	p.Thr2043Thr	synonymous_variant	42/55	ENST00000262715.10	NP_009041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10	c.6129G>A	p.Thr2043Thr	synonymous_variant	42/55	1	NM_007110.5	ENSP00000262715.5

Frequencies

GnomAD3 genomes AF: 0.0462 AC: 7034 AN: 152148 Hom.: 227 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0951

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0610

Gnomad OTH AF: 0.0494

GnomAD3 exomes AF: 0.0547 AC: 13742 AN: 251154 Hom.: 511 AF XY: 0.0591 AC XY: 8020 AN XY: 135770

Gnomad AFR exome AF: 0.0182

Gnomad AMR exome AF: 0.0278

Gnomad ASJ exome AF: 0.0764

Gnomad EAS exome AF: 0.000598

Gnomad SAS exome AF: 0.0952

Gnomad FIN exome AF: 0.0687

Gnomad NFE exome AF: 0.0614

Gnomad OTH exome AF: 0.0552

GnomAD4 exome AF: 0.0626 AC: 91537 AN: 1461834 Hom.: 3109 Cov.: 32 AF XY: 0.0640 AC XY: 46530 AN XY: 727224

Gnomad4 AFR exome AF: 0.0169

Gnomad4 AMR exome AF: 0.0291

Gnomad4 ASJ exome AF: 0.0761

Gnomad4 EAS exome AF: 0.000327

Gnomad4 SAS exome AF: 0.0930

Gnomad4 FIN exome AF: 0.0663

Gnomad4 NFE exome AF: 0.0649

Gnomad4 OTH exome AF: 0.0573

GnomAD4 genome AF: 0.0462 AC: 7035 AN: 152266 Hom.: 227 Cov.: 32 AF XY: 0.0471 AC XY: 3509 AN XY: 74448

Gnomad4 AFR AF: 0.0180

Gnomad4 AMR AF: 0.0358

Gnomad4 ASJ AF: 0.0723

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0950

Gnomad4 FIN AF: 0.0686

Gnomad4 NFE AF: 0.0610

Gnomad4 OTH AF: 0.0489

Alfa AF: 0.0570 Hom.: 223

Bravo AF: 0.0416

Asia WGS AF: 0.0350 AC: 122 AN: 3478

EpiCase AF: 0.0632

EpiControl AF: 0.0626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.44
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2228042; hg19: chr14-20844383;