rs118141823

Positions:

chr14-102434619-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014844.5(TECPR2):c.1802C>T(p.Pro601Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,583,794 control chromosomes in the GnomAD database, including 353 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P601P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.016 ( 29 hom., cov: 32)

Exomes 𝑓: 0.020 ( 324 hom. )

Consequence

TECPR2
NM_014844.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0500

Variant links:

Genes affected

TECPR2 (HGNC:19957): (tectonin beta-propeller repeat containing 2) The protein encoded by this gene is a member of the tectonin beta-propeller repeat-containing (TECPR) family, and contains both TECPR and tryptophan-aspartic acid repeat (WD repeat) domains. This gene has been implicated in autophagy, as reduced expression levels of this gene have been associated with impaired autophagy. Recessive mutations in this gene have been associated with a hereditary form of spastic paraparesis (HSP). HSP is characterized by progressive spasticity and paralysis of the legs. There is also some evidence linking mutations in this gene with birdshot chorioretinopathy (BSCR), which results in inflammation of the choroid and retina. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

TECPR2 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 (MetaRNN=0.002579838).

BP6

Variant 14-102434619-C-T is Benign according to our data. Variant chr14-102434619-C-T is described in ClinVar as [Benign]. Clinvar id is 220729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-102434619-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0165 (2506/152272) while in subpopulation AMR AF= 0.0281 (429/15294). AF 95% confidence interval is 0.0259. There are 29 homozygotes in gnomad4. There are 1195 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECPR2	NM_014844.5 linkuse as main transcript	c.1802C>T	p.Pro601Leu	missense_variant	9/20	ENST00000359520.12
TECPR2	NM_001172631.3 linkuse as main transcript	c.1802C>T	p.Pro601Leu	missense_variant	9/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECPR2	ENST00000359520.12 linkuse as main transcript	c.1802C>T	p.Pro601Leu	missense_variant	9/20	1	NM_014844.5	P1	O15040-1
TECPR2	ENST00000558678.1 linkuse as main transcript	c.1802C>T	p.Pro601Leu	missense_variant	9/17	1			O15040-2

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2510

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00393

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0281

Gnomad ASJ

AF:

0.0332

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.0109

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0227

Gnomad OTH

AF:

0.0229

GnomAD3 exomes

AF:

0.0165

AC:

3847

AN:

233650

Hom.:

AF XY:

0.0165

AC XY:

2068

AN XY:

125220

show subpopulations

Gnomad AFR exome

AF:

0.00453

Gnomad AMR exome

AF:

0.0202

Gnomad ASJ exome

AF:

0.0298

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00747

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0215

Gnomad OTH exome

AF:

0.0267

GnomAD4 exome

AF:

0.0197

AC:

28271

AN:

1431522

Hom.:

324

Cov.:

AF XY:

0.0194

AC XY:

13689

AN XY:

707384

show subpopulations

Gnomad4 AFR exome

AF:

0.00360

Gnomad4 AMR exome

AF:

0.0208

Gnomad4 ASJ exome

AF:

0.0324

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00834

Gnomad4 FIN exome

AF:

0.0142

Gnomad4 NFE exome

AF:

0.0218

Gnomad4 OTH exome

AF:

0.0196

GnomAD4 genome

AF:

0.0165

AC:

2506

AN:

152272

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1195

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00392

Gnomad4 AMR

AF:

0.0281

Gnomad4 ASJ

AF:

0.0332

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00787

Gnomad4 FIN

AF:

0.0109

Gnomad4 NFE

AF:

0.0227

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0206

Hom.:

Bravo

AF:

0.0174

TwinsUK

AF:

0.0175

AC:

ALSPAC

AF:

0.0257

AC:

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.0229

AC:

197

ExAC

AF:

0.0165

AC:

2002

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2016

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. -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Aug 30, 2021

- -

Hereditary spastic paraplegia 49

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.5

DANN

Benign

0.96

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.046

Sift

Uncertain

0.021

D;D

Sift4G

Benign

0.49

T;T

Polyphen

0.0040

B;.

Vest4

0.022

MPC

0.31

ClinPred

0.0062

GERP RS

-0.26

Varity_R

0.032

gMVP

0.20

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