6-42923128-C-T

Variant summary

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

The NM_138296.3(PTCRA):​c.160C>T​(p.Pro54Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000768 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

PTCRA
NM_138296.3 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.514
Variant links:
Genes affected
PTCRA (HGNC:21290): (pre T cell antigen receptor alpha) The protein encoded by this gene is a single-pass type I membrane protein that is found in immmature but not mature T-cells. Along with TCRB and CD3 complex, the encoded protein forms the pre-T-cell receptor complex, which regulates early T-cell development. Four transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

Genome browser will be placed here

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=0.13992932).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTCRANM_138296.3 linkc.160C>T p.Pro54Ser missense_variant Exon 2 of 4 ENST00000304672.6 NP_612153.2 Q6ISU1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTCRAENST00000304672.6 linkc.160C>T p.Pro54Ser missense_variant Exon 2 of 4 1 NM_138296.3 ENSP00000304447.2 Q6ISU1-1
PTCRAENST00000441198.4 linkc.102-17C>T intron_variant Intron 2 of 4 1 ENSP00000409550.1 Q6ISU1-3
PTCRAENST00000446507.5 linkc.59-1101C>T intron_variant Intron 1 of 2 1 ENSP00000392288.1 Q6ISU1-2
PTCRAENST00000616441.2 linkc.160C>T p.Pro54Ser missense_variant Exon 2 of 4 2 ENSP00000477815.1 A0A087WTE9

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152224
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251394
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135886
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:
0.0000440
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000814
AC:
119
AN:
1461876
Hom.:
0
Cov.:
32
AF XY:
0.0000729
AC XY:
53
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000103
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152224
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000579
Hom.:
0
Bravo
AF:
0.0000604
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 07, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.160C>T (p.P54S) alteration is located in exon 2 (coding exon 2) of the PTCRA gene. This alteration results from a C to T substitution at nucleotide position 160, causing the proline (P) at amino acid position 54 to be replaced by a serine (S). 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
0.13
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.39
T;.
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L;.
PrimateAI
Benign
0.30
T
PROVEAN
Pathogenic
-4.5
D;.
REVEL
Benign
0.20
Sift
Benign
0.040
D;.
Sift4G
Uncertain
0.049
D;D
Polyphen
0.59
P;.
Vest4
0.22
MVP
0.57
MPC
0.18
ClinPred
0.077
T
GERP RS
4.0
Varity_R
0.20
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs146960695; hg19: chr6-42890866; API