rs1713449

Variant names:

• chr14-20373548-C-G
• rs1713449
• NM_007110.5:c.6640G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-20373548-C-G
• chr14-20373548-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007110.5(TEP1):​c.6640G>C​(p.Val2214Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TEP1 NM_007110.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1697216).

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.6640G>C	p.Val2214Leu	missense	Exon 46 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.6316G>C	p.Val2106Leu	missense	Exon 44 of 53	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.6640G>C	p.Val2214Leu	missense	Exon 46 of 55	ENSP00000262715.5	Q99973-1
	TEP1	ENST00000556935.5	TSL:1	c.6316G>C	p.Val2106Leu	missense	Exon 44 of 53	ENSP00000452574.1	G3V5X7
	TEP1	ENST00000555008.5	TSL:1	n.4669G>C		non_coding_transcript_exon	Exon 34 of 43	ENSP00000450541.1	G3V2A4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.5
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.060
Sift	Benign	0.15	T
Sift4G	Benign	0.061	T
Polyphen		0.0090	B
Vest4		0.38
MutPred		0.63		Gain of sheet (P = 0.0827)
MVP		0.14
MPC		0.12
ClinPred		0.046	T
GERP RS		4.3
PromoterAI		-0.061	Neutral
Varity_R		0.043
gMVP		0.44
Mutation Taster		=94/6	polymorphism

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: rs1713449; hg19: chr14-20841707;