14-20368894-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007110.5(TEP1):c.7665G>A(p.Ser2555=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,613,320 control chromosomes in the GnomAD database, including 300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (151 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (149 hom.)
• Consequence: TEP1 NM_007110.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.77

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 -10 ACMG points.

• BP6: Variant 14-20368894-C-T is Benign according to our data. Variant chr14-20368894-C-T is described in ClinVar as [Benign]. Clinvar id is 779653.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEP1	NM_007110.5	c.7665G>A	p.Ser2555=	synonymous_variant	54/55	ENST00000262715.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEP1	ENST00000262715.10	c.7665G>A	p.Ser2555=	synonymous_variant	54/55	1	NM_007110.5	P1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3669 AN: 152090 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.00632 AC: 1578 AN: 249744 Hom.: 66 AF XY: 0.00440 AC XY: 594 AN XY: 134952

Gnomad AFR exome AF: 0.0842

Gnomad AMR exome AF: 0.00471

Gnomad ASJ exome AF: 0.000996

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000198

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000266

Gnomad OTH exome AF: 0.00246

GnomAD4 exome AF: 0.00255 AC: 3728 AN: 1461116 Hom.: 149 Cov.: 34 AF XY: 0.00215 AC XY: 1566 AN XY: 726824

Gnomad4 AFR exome AF: 0.0845

Gnomad4 AMR exome AF: 0.00509

Gnomad4 ASJ exome AF: 0.00134

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000221

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000219

Gnomad4 OTH exome AF: 0.00562

GnomAD4 genome AF: 0.0241 AC: 3673 AN: 152204 Hom.: 151 Cov.: 32 AF XY: 0.0231 AC XY: 1723 AN XY: 74440

Gnomad4 AFR AF: 0.0838

Gnomad4 AMR AF: 0.00804

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.00166 Hom.: 2

Bravo AF: 0.0279

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	21
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.65		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.65		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2228034; hg19: chr14-20837053;