14-20384108-C-T

Variant names:

• chr14-20384108-C-T
• rs2228041
• NM_007110.5:c.3464G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007110.5(TEP1):​c.3464G>A​(p.Arg1155Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0564 in 1,613,998 control chromosomes in the GnomAD database, including 2,909 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 𝑓 0.042 (180 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2729 hom.)
• Consequence: TEP1 NM_007110.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016416013).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0849 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.3464G>A	p.Arg1155Gln	missense	Exon 24 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.3140G>A	p.Arg1047Gln	missense	Exon 22 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.3464G>A	p.Arg1155Gln	missense	Exon 24 of 55	ENSP00000262715.5	Q99973-1
	TEP1	ENST00000556935.5	TSL:1	c.3140G>A	p.Arg1047Gln	missense	Exon 22 of 53	ENSP00000452574.1	G3V5X7
	TEP1	ENST00000555008.5	TSL:1	n.1514G>A		non_coding_transcript_exon	Exon 12 of 43	ENSP00000450541.1	G3V2A4

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6397 AN: 152130 Hom.: 180 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0928

Gnomad FIN AF: 0.0702

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.0464

GnomAD2 exomes AF: 0.0515 AC: 12936 AN: 251066 AF XY: 0.0558

Gnomad AFR exome AF: 0.00973

Gnomad AMR exome AF: 0.0249

Gnomad ASJ exome AF: 0.0574

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.0708

Gnomad NFE exome AF: 0.0585

Gnomad OTH exome AF: 0.0552

GnomAD4 exome AF: 0.0579 AC: 84636 AN: 1461750 Hom.: 2729 Cov.: 36 AF XY: 0.0594 AC XY: 43196 AN XY: 727190

African (AFR) AF: 0.00902 AC: 302 AN: 33480

American (AMR) AF: 0.0268 AC: 1197 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0570 AC: 1489 AN: 26132

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39700

South Asian (SAS) AF: 0.0905 AC: 7807 AN: 86256

European-Finnish (FIN) AF: 0.0665 AC: 3544 AN: 53292

Middle Eastern (MID) AF: 0.0751 AC: 433 AN: 5768

European-Non Finnish (NFE) AF: 0.0599 AC: 66589 AN: 1112004

Other (OTH) AF: 0.0539 AC: 3255 AN: 60396

GnomAD4 genome AF: 0.0420 AC: 6393 AN: 152248 Hom.: 180 Cov.: 32 AF XY: 0.0430 AC XY: 3201 AN XY: 74432

African (AFR) AF: 0.0110 AC: 456 AN: 41552

American (AMR) AF: 0.0332 AC: 507 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0920 AC: 444 AN: 4826

European-Finnish (FIN) AF: 0.0702 AC: 744 AN: 10598

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0575 AC: 3908 AN: 68016

Other (OTH) AF: 0.0459 AC: 97 AN: 2114

Alfa AF: 0.0509 Hom.: 632

Bravo AF: 0.0364

TwinsUK AF: 0.0601 AC: 223

ALSPAC AF: 0.0566 AC: 218

ESP6500AA AF: 0.0113 AC: 50

ESP6500EA AF: 0.0617 AC: 531

ExAC AF: 0.0521 AC: 6326

Asia WGS AF: 0.0340 AC: 119 AN: 3478

EpiCase AF: 0.0592

EpiControl AF: 0.0584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.7
DANN	Benign	0.22
DEOGEN2	Benign	0.057	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.5	N
PhyloP100		0.44
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.097
MPC		0.13
ClinPred		0.0021	T
GERP RS		0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.015
gMVP		0.098
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: rs2228041; hg19: chr14-20852267;