Genetic Variant NM_138296.3:c.103C>G (chr6-42923071-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_138296.3(PTCRA):c.103C>G(p.Leu35Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PTCRA
NM_138296.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.864

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16185835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCRA	NM_138296.3 link	c.103C>G	p.Leu35Val	missense_variant	Exon 2 of 4	ENST00000304672.6	NP_612153.2	Q6ISU1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTCRA	ENST00000304672.6 link	c.103C>G	p.Leu35Val	missense_variant	Exon 2 of 4	1	NM_138296.3	ENSP00000304447.2	Q6ISU1-1
PTCRA	ENST00000441198.4 link	c.102-74C>G		intron_variant	Intron 2 of 4	1		ENSP00000409550.1	Q6ISU1-3
PTCRA	ENST00000446507.5 link	c.59-1158C>G		intron_variant	Intron 1 of 2	1		ENSP00000392288.1	Q6ISU1-2
PTCRA	ENST00000616441.2 link	c.103C>G	p.Leu35Val	missense_variant	Exon 2 of 4	2		ENSP00000477815.1	A0A087WTE9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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

Apr 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.103C>G (p.L35V) alteration is located in exon 2 (coding exon 2) of the PTCRA gene. This alteration results from a C to G substitution at nucleotide position 103, causing the leucine (L) at amino acid position 35 to be replaced by a valine (V). 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

0.17

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.1

N;.

REVEL

Benign

0.064

Sift

Uncertain

0.016

D;.

Sift4G

Uncertain

0.016

D;D

Polyphen

0.92

P;.

Vest4

0.21

MutPred

0.27

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.83

MPC

0.39

ClinPred

0.54

GERP RS

3.9

Varity_R

0.37

gMVP

0.29

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

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