Genetic Variant TECPR1:p.Val1083Met (chr7-98217953-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015395.3(TECPR1):c.3247G>A(p.Val1083Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000835 in 1,556,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

TECPR1
NM_015395.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECPR1	NM_015395.3 link	c.3247G>A	p.Val1083Met	missense_variant	Exon 24 of 26	ENST00000447648.7	NP_056210.1	Q7Z6L1-1
TECPR1	XM_005250253.5 link	c.3247G>A	p.Val1083Met	missense_variant	Exon 24 of 26		XP_005250310.1	Q7Z6L1-1
TECPR1	XM_017011937.2 link	c.3145G>A	p.Val1049Met	missense_variant	Exon 23 of 25		XP_016867426.1
TECPR1	XM_047420119.1 link	c.3145G>A	p.Val1049Met	missense_variant	Exon 23 of 25		XP_047276075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECPR1	ENST00000447648.7 link	c.3247G>A	p.Val1083Met	missense_variant	Exon 24 of 26	1	NM_015395.3	ENSP00000404923.2		Q7Z6L1-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000854

AC:

AN:

1404546

Hom.:

Cov.:

AF XY:

0.00000721

AC XY:

AN XY:

693358

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000829

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000739

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3247G>A (p.V1083M) alteration is located in exon 24 (coding exon 22) of the TECPR1 gene. This alteration results from a G to A substitution at nucleotide position 3247, causing the valine (V) at amino acid position 1083 to be replaced by a methionine (M). 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

0.33

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.031

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.34

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.65

MutPred

0.85

Loss of sheet (P = 0.0457);

MVP

0.70

MPC

0.55

ClinPred

0.96

GERP RS

4.6

Varity_R

0.16

gMVP

0.57

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