Variant 6-42925339-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138296.3(PTCRA):c.503C>A(p.Thr168Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

PTCRA
NM_138296.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.755

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]

PTCRA links:

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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	Protein	UniProt
PTCRA	NM_138296.3 link	c.503C>A	p.Thr168Asn	missense_variant	4/4	ENST00000304672.6	NP_612153.2	Q6ISU1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PTCRA	ENST00000304672.6 link	c.503C>A	p.Thr168Asn	missense_variant	4/4	1	NM_138296.3	ENSP00000304447.2	Q6ISU1-1
PTCRA	ENST00000441198.4 link	c.428C>A	p.Thr143Asn	missense_variant	5/5	1		ENSP00000409550.1	Q6ISU1-3
PTCRA	ENST00000446507.5 link	c.182C>A	p.Thr61Asn	missense_variant	3/3	1		ENSP00000392288.1	Q6ISU1-2
PTCRA	ENST00000616441.2 link	c.548C>A	p.Thr183Asn	missense_variant	4/4	2		ENSP00000477815.1	A0A087WTE9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1424052

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000247

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 29, 2023

The c.503C>A (p.T168N) alteration is located in exon 4 (coding exon 4) of the PTCRA gene. This alteration results from a C to A substitution at nucleotide position 503, causing the threonine (T) at amino acid position 168 to be replaced by an asparagine (N). 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

Pathogenic

0.66

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

T;.;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.56

T;T;T;T

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.52

D;D;D;D

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.9

L;.;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.7

D;D;D;.

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.65

MutPred

0.36

Gain of loop (P = 0.0195);.;.;.;

MVP

0.76

MPC

0.66

ClinPred

0.99

GERP RS

5.3

Varity_R

0.75

gMVP

0.51

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over