7-98217953-C-T

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

1
9
9

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]

Genome browser will be placed here

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
TECPR1NM_015395.3 linkc.3247G>A p.Val1083Met missense_variant Exon 24 of 26 ENST00000447648.7 NP_056210.1 Q7Z6L1-1
TECPR1XM_005250253.5 linkc.3247G>A p.Val1083Met missense_variant Exon 24 of 26 XP_005250310.1 Q7Z6L1-1
TECPR1XM_017011937.2 linkc.3145G>A p.Val1049Met missense_variant Exon 23 of 25 XP_016867426.1
TECPR1XM_047420119.1 linkc.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
TECPR1ENST00000447648.7 linkc.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:
1
AN:
152250
Hom.:
0
Cov.:
33
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:
12
AN:
1404546
Hom.:
0
Cov.:
34
AF XY:
0.00000721
AC XY:
5
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:
1
AN:
152250
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
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
T
BayesDel_noAF
Benign
-0.26
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.031
D
MetaRNN
Pathogenic
0.85
D
MetaSVM
Benign
-0.34
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.5
N
REVEL
Uncertain
0.34
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.011
D
Polyphen
1.0
D
Vest4
0.65
MutPred
0.85
Loss of sheet (P = 0.0457);
MVP
0.70
MPC
0.55
ClinPred
0.96
D
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.

Other links and lift over

dbSNP: rs1427897115; hg19: chr7-97847265; API