Variant rs2072651 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000391.4(TPP1):c.1075+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,611,728 control chromosomes in the GnomAD database, including 24,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2856 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22088 hom. )

Consequence

TPP1
NM_000391.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.320

Variant links:

Genes affected

TPP1 (HGNC:2073): (tripeptidyl peptidase 1) This gene encodes a member of the sedolisin family of serine proteases. The protease functions in the lysosome to cleave N-terminal tripeptides from substrates, and has weaker endopeptidase activity. It is synthesized as a catalytically-inactive enzyme which is activated and auto-proteolyzed upon acidification. Mutations in this gene result in late-infantile neuronal ceroid lipofuscinosis, which is associated with the failure to degrade specific neuropeptides and a subunit of ATP synthase in the lysosome. [provided by RefSeq, Jul 2008]

TPP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 11-6616273-G-A is Benign according to our data. Variant chr11-6616273-G-A is described in ClinVar as [Benign]. Clinvar id is 670738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-6616273-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPP1	NM_000391.4 linkuse as main transcript	c.1075+42C>T		intron_variant		ENST00000299427.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPP1	ENST00000299427.12 linkuse as main transcript	c.1075+42C>T		intron_variant		1	NM_000391.4	P1	O14773-1

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28748

AN:

152034

Hom.:

2855

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.199

GnomAD3 exomes

AF:

0.188

AC:

47001

AN:

249540

Hom.:

4733

AF XY:

0.187

AC XY:

25251

AN XY:

134988

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.334

Gnomad SAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.170

AC:

248530

AN:

1459576

Hom.:

22088

Cov.:

AF XY:

0.171

AC XY:

123876

AN XY:

726184

show subpopulations

Gnomad4 AFR exome

AF:

0.215

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.332

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.189

AC:

28775

AN:

152152

Hom.:

2856

Cov.:

AF XY:

0.189

AC XY:

14059

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.208

Gnomad4 ASJ

AF:

0.247

Gnomad4 EAS

AF:

0.341

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.175

Hom.:

4476

Bravo

AF:

0.196

Asia WGS

AF:

0.236

AC:

822

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 34% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 32. Only high quality variants are reported. -

Autosomal recessive spinocerebellar ataxia 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Neuronal ceroid lipofuscinosis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.4

DANN

Benign

0.38

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over