Variant 7-98221697-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015395.3(TECPR1):c.3121G>A(p.Ala1041Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,613,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

TECPR1
NM_015395.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68

Variant links:

Genes affected

TECPR1 (HGNC:22214): (tectonin beta-propeller repeat containing 1) This gene encodes a tethering factor involved in autophagy. The encoded protein is found at autolysosomes, and is involved in targeting protein aggregates, damaged mitochondria, and bacterial pathogens for autophagy [provided by RefSeq, Nov 2012]

TECPR1 links:

TECPR1 (HGNC:):

TECPR1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25098905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECPR1	NM_015395.3 linkuse as main transcript	c.3121G>A	p.Ala1041Thr	missense_variant	23/26	ENST00000447648.7	NP_056210.1	Q7Z6L1-1
TECPR1	XM_005250253.5 linkuse as main transcript	c.3121G>A	p.Ala1041Thr	missense_variant	23/26		XP_005250310.1	Q7Z6L1-1
TECPR1	XM_017011937.2 linkuse as main transcript	c.3019G>A	p.Ala1007Thr	missense_variant	22/25		XP_016867426.1
TECPR1	XM_047420119.1 linkuse as main transcript	c.3019G>A	p.Ala1007Thr	missense_variant	22/25		XP_047276075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECPR1	ENST00000447648.7 linkuse as main transcript	c.3121G>A	p.Ala1041Thr	missense_variant	23/26	1	NM_015395.3	ENSP00000404923.2		Q7Z6L1-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000482

AC:

AN:

249030

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135200

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000527

AC:

AN:

1461288

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000612

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000578

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 05, 2022

The c.3121G>A (p.A1041T) alteration is located in exon 23 (coding exon 21) of the TECPR1 gene. This alteration results from a G to A substitution at nucleotide position 3121, causing the alanine (A) at amino acid position 1041 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.088

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.055

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.34

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.75

REVEL

Uncertain

0.31

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.016

Polyphen

0.0090

Vest4

0.35

MutPred

0.40

Loss of helix (P = 0.028);

MVP

0.63

MPC

0.23

ClinPred

0.22

GERP RS

4.5

Varity_R

0.22

gMVP

0.28

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