rs1760898

Variant names:

• chr14-20404722-G-T
• rs1760898
• NM_007110.5:c.921C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-20404722-G-T
• chr14-20404722-G-A
• chr14-20404722-G-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.921C>A​(p.Asn307Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,613,300 control chromosomes in the GnomAD database, including 54,837 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8169 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46668 hom.)
• Consequence: TEP1 NM_007110.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00100
• Publications: 40 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]

TEP1 Gene-Disease associations (from GenCC):

• cerebral palsy

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.589238E-5).
• BP6: Variant 14-20404722-G-T is Benign according to our data. Variant chr14-20404722-G-T is described in ClinVar as Benign. ClinVar VariationId is 1232904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007110.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	NM_007110.5	MANE Select	c.921C>A	p.Asn307Lys	missense	Exon 5 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.870+729C>A		intron	N/A	NP_001305964.1	G3V5X7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	ENST00000262715.10	TSL:1 MANE Select	c.921C>A	p.Asn307Lys	missense	Exon 5 of 55	ENSP00000262715.5	Q99973-1
	TEP1	ENST00000556935.5	TSL:1	c.870+729C>A		intron	N/A	ENSP00000452574.1	G3V5X7
	TEP1	ENST00000555727.5	TSL:1	n.921C>A		non_coding_transcript_exon	Exon 5 of 54	ENSP00000451634.1	G3V470

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46892 AN: 152012 Hom.: 8145 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.282

GnomAD2 exomes AF: 0.286 AC: 71713 AN: 250698 AF XY: 0.279

Gnomad AFR exome AF: 0.472

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.268

Gnomad EAS exome AF: 0.441

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.216

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.245 AC: 358282 AN: 1461170 Hom.: 46668 Cov.: 33 AF XY: 0.245 AC XY: 178122 AN XY: 726888

African (AFR) AF: 0.480 AC: 16076 AN: 33462

American (AMR) AF: 0.343 AC: 15288 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 7164 AN: 26120

East Asian (EAS) AF: 0.383 AC: 15177 AN: 39642

South Asian (SAS) AF: 0.329 AC: 28341 AN: 86160

European-Finnish (FIN) AF: 0.225 AC: 11995 AN: 53390

Middle Eastern (MID) AF: 0.197 AC: 1138 AN: 5764

European-Non Finnish (NFE) AF: 0.222 AC: 247062 AN: 1111654

Other (OTH) AF: 0.266 AC: 16041 AN: 60354

GnomAD4 genome AF: 0.309 AC: 46977 AN: 152130 Hom.: 8169 Cov.: 32 AF XY: 0.309 AC XY: 23007 AN XY: 74362

African (AFR) AF: 0.466 AC: 19328 AN: 41490

American (AMR) AF: 0.304 AC: 4651 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3466

East Asian (EAS) AF: 0.428 AC: 2214 AN: 5172

South Asian (SAS) AF: 0.329 AC: 1592 AN: 4832

European-Finnish (FIN) AF: 0.225 AC: 2382 AN: 10588

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14920 AN: 67982

Other (OTH) AF: 0.283 AC: 596 AN: 2108

Alfa AF: 0.252 Hom.: 17852

Bravo AF: 0.320

TwinsUK AF: 0.221 AC: 821

ALSPAC AF: 0.210 AC: 811

ESP6500AA AF: 0.451 AC: 1989

ESP6500EA AF: 0.217 AC: 1865

ExAC AF: 0.286 AC: 34693

Asia WGS AF: 0.395 AC: 1374 AN: 3478

EpiCase AF: 0.218

EpiControl AF: 0.221

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.7
DANN	Benign	0.94
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.053	T
MetaRNN	Benign	0.000096	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.3	N
PhyloP100		-0.0010
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.74	N
REVEL	Benign	0.014
Sift	Benign	0.30	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.065
MutPred		0.44		Gain of MoRF binding (P = 0.0353)
MPC		0.13
ClinPred		0.0056	T
GERP RS		-0.96
Varity_R		0.030
gMVP		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1760898; hg19: chr14-20872881; COSMIC: COSV52990468; COSMIC: COSV52990468;