1-3628538-A-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_182752.4(TPRG1L):c.754A>T(p.Met252Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,406 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
TPRG1L
NM_182752.4 missense
NM_182752.4 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 7.17
Genes affected
TPRG1L (HGNC:27007): (tumor protein p63 regulated 1 like) Predicted to enable identical protein binding activity. Predicted to be involved in regulation of glutamatergic synaptic transmission. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPRG1L | NM_182752.4 | c.754A>T | p.Met252Leu | missense_variant | 5/5 | ENST00000378344.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPRG1L | ENST00000378344.7 | c.754A>T | p.Met252Leu | missense_variant | 5/5 | 2 | NM_182752.4 | P1 | |
TPRG1L | ENST00000344579.5 | c.577A>T | p.Met193Leu | missense_variant | 4/4 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151866Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
1
AN:
151866
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251168Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135832
GnomAD3 exomes
AF:
AC:
2
AN:
251168
Hom.:
AF XY:
AC XY:
1
AN XY:
135832
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461540Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727046
GnomAD4 exome
AF:
AC:
14
AN:
1461540
Hom.:
Cov.:
30
AF XY:
AC XY:
6
AN XY:
727046
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151866Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74170
GnomAD4 genome
AF:
AC:
1
AN:
151866
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74170
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
EpiCase
AF:
EpiControl
AF:
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 | Dec 13, 2022 | The c.754A>T (p.M252L) alteration is located in exon 5 (coding exon 5) of the TPRG1L gene. This alteration results from a A to T substitution at nucleotide position 754, causing the methionine (M) at amino acid position 252 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;D
Polyphen
P;P
Vest4
MutPred
Gain of helix (P = 0.132);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at