14-20383870-A-G

Variant names:

• chr14-20383870-A-G
• rs1760904
• NM_007110.5:c.3583T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007110.5(TEP1):​c.3583T>C​(p.Ser1195Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,600,432 control chromosomes in the GnomAD database, including 215,998 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (31645 hom., cov: 32)
  • Exomes 𝑓: 0.50 (184353 hom.)
• Consequence: TEP1 NM_007110.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.936
• Publications: 45 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.419641E-7).
• BP6: Variant 14-20383870-A-G is Benign according to our data. Variant chr14-20383870-A-G is described in ClinVar as Benign. ClinVar VariationId is 1183378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEP1	NM_007110.5	c.3583T>C	p.Ser1195Pro	missense_variant	Exon 25 of 55	ENST00000262715.10	NP_009041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10	c.3583T>C	p.Ser1195Pro	missense_variant	Exon 25 of 55	1	NM_007110.5	ENSP00000262715.5
TEP1	ENST00000556935.5	c.3259T>C	p.Ser1087Pro	missense_variant	Exon 23 of 53	1		ENSP00000452574.1
TEP1	ENST00000555008.5	n.1633T>C		non_coding_transcript_exon_variant	Exon 13 of 43	1		ENSP00000450541.1
TEP1	ENST00000555727.5	n.3583T>C		non_coding_transcript_exon_variant	Exon 25 of 54	1		ENSP00000451634.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93719 AN: 151928 Hom.: 31582 Cov.: 32

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.606

GnomAD2 exomes AF: 0.558 AC: 131324 AN: 235410 AF XY: 0.548

Gnomad AFR exome AF: 0.906

Gnomad AMR exome AF: 0.655

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.629

Gnomad FIN exome AF: 0.446

Gnomad NFE exome AF: 0.465

Gnomad OTH exome AF: 0.534

GnomAD4 exome AF: 0.497 AC: 719322 AN: 1448386 Hom.: 184353 Cov.: 65 AF XY: 0.499 AC XY: 359629 AN XY: 720360

African (AFR) AF: 0.917 AC: 30668 AN: 33444

American (AMR) AF: 0.651 AC: 28503 AN: 43774

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 13523 AN: 26018

East Asian (EAS) AF: 0.602 AC: 23791 AN: 39538

South Asian (SAS) AF: 0.637 AC: 54500 AN: 85544

European-Finnish (FIN) AF: 0.447 AC: 19636 AN: 43956

Middle Eastern (MID) AF: 0.556 AC: 3206 AN: 5764

European-Non Finnish (NFE) AF: 0.463 AC: 513809 AN: 1110094

Other (OTH) AF: 0.526 AC: 31686 AN: 60254

GnomAD4 genome AF: 0.617 AC: 93835 AN: 152046 Hom.: 31645 Cov.: 32 AF XY: 0.616 AC XY: 45746 AN XY: 74308

African (AFR) AF: 0.905 AC: 37548 AN: 41508

American (AMR) AF: 0.619 AC: 9456 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1801 AN: 3468

East Asian (EAS) AF: 0.626 AC: 3236 AN: 5166

South Asian (SAS) AF: 0.644 AC: 3096 AN: 4810

European-Finnish (FIN) AF: 0.461 AC: 4866 AN: 10548

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32040 AN: 67950

Other (OTH) AF: 0.612 AC: 1292 AN: 2112

Alfa AF: 0.515 Hom.: 91147

Bravo AF: 0.637

TwinsUK AF: 0.454 AC: 1682

ALSPAC AF: 0.473 AC: 1823

ESP6500AA AF: 0.889 AC: 3918

ESP6500EA AF: 0.472 AC: 4060

ExAC AF: 0.552 AC: 66862

Asia WGS AF: 0.702 AC: 2440 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 19, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.037
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.18
DEOGEN2	Benign	0.084	T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.059	T;T
MetaRNN	Benign	7.4e-7	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.3	N;.
PhyloP100		0.94
PrimateAI	Benign	0.44	T
PROVEAN	Benign	1.7	N;N
REVEL	Benign	0.16
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.13
ClinPred		0.0015	T
GERP RS		4.8
Varity_R		0.074
gMVP		0.50
Mutation Taster		=98/2	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: rs1760904; hg19: chr14-20852029; COSMIC: COSV52991059; COSMIC: COSV52991059;