rs11845676

Positions:

Variant summary

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

The NM_014844.5(TECPR2):c.1156G>A(p.Ala386Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,603,288 control chromosomes in the GnomAD database, including 613 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 306 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 307 hom. )

Consequence

TECPR2
NM_014844.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.654

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=0.0017033517).

BP6

Variant 14-102431867-G-A is Benign according to our data. Variant chr14-102431867-G-A is described in ClinVar as [Benign]. Clinvar id is 415302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-102431867-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECPR2	NM_014844.5 linkuse as main transcript	c.1156G>A	p.Ala386Thr	missense_variant	8/20	ENST00000359520.12	NP_055659.2	O15040-1
TECPR2	NM_001172631.3 linkuse as main transcript	c.1156G>A	p.Ala386Thr	missense_variant	8/17		NP_001166102.1	O15040-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECPR2	ENST00000359520.12 linkuse as main transcript	c.1156G>A	p.Ala386Thr	missense_variant	8/20	1	NM_014844.5	ENSP00000352510.7		O15040-1
TECPR2	ENST00000558678.1 linkuse as main transcript	c.1156G>A	p.Ala386Thr	missense_variant	8/17	1		ENSP00000453671.1		O15040-2

Frequencies

GnomAD3 genomes

AF:

0.0382

AC:

5817

AN:

152204

Hom.:

306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0192

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00561

Gnomad OTH

AF:

0.0315

GnomAD3 exomes

AF:

0.0138

AC:

3437

AN:

248572

Hom.:

135

AF XY:

0.0113

AC XY:

1521

AN XY:

134572

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.0244

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00236

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.00587

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.00904

AC:

13115

AN:

1450966

Hom.:

307

Cov.:

AF XY:

0.00838

AC XY:

6027

AN XY:

719078

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.0122

Gnomad4 ASJ exome

AF:

0.0249

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00258

Gnomad4 FIN exome

AF:

0.00152

Gnomad4 NFE exome

AF:

0.00613

Gnomad4 OTH exome

AF:

0.0133

GnomAD4 genome

AF:

0.0382

AC:

5822

AN:

152322

Hom.:

306

Cov.:

AF XY:

0.0370

AC XY:

2753

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.0191

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00562

Gnomad4 OTH

AF:

0.0312

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0439

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.123

AC:

541

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.0157

AC:

1910

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.00763

EpiControl

AF:

0.00753

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 49

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 20, 2017

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

Dec 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.7

DANN

Benign

0.96

DEOGEN2

Benign

0.0022

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.79

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.21

N;N

REVEL

Benign

0.043

Sift

Benign

0.54

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0010

B;.

Vest4

0.021

MPC

0.30

ClinPred

0.0024

GERP RS

4.2

Varity_R

0.025

gMVP

0.26

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