6-42925328-C-G

Variant names:

• chr6-42925328-C-G
• NM_138296.3:c.492C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138296.3(PTCRA):​c.492C>G​(p.Asp164Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTCRA NM_138296.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.66

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]

ACMG classification

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=0.21849045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCRA	NM_138296.3	c.492C>G	p.Asp164Glu	missense_variant	Exon 4 of 4	ENST00000304672.6	NP_612153.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCRA	ENST00000304672.6	c.492C>G	p.Asp164Glu	missense_variant	Exon 4 of 4	1	NM_138296.3	ENSP00000304447.2
PTCRA	ENST00000441198.4	c.417C>G	p.Asp139Glu	missense_variant	Exon 5 of 5	1		ENSP00000409550.1
PTCRA	ENST00000446507.5	c.171C>G	p.Asp57Glu	missense_variant	Exon 3 of 3	1		ENSP00000392288.1
PTCRA	ENST00000616441.2	c.537C>G	p.Asp179Glu	missense_variant	Exon 4 of 4	2		ENSP00000477815.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.492C>G (p.D164E) alteration is located in exon 4 (coding exon 4) of the PTCRA gene. This alteration results from a C to G substitution at nucleotide position 492, causing the aspartic acid (D) at amino acid position 164 to be replaced by a glutamic acid (E). 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	0.89
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D;.;.;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.51	T;T;T;T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	L;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.1	D;D;D;.
REVEL	Benign	0.20
Sift	Benign	0.038	D;D;T;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.38
MutPred		0.46		Gain of helix (P = 0.0696);.;.;.;
MVP		0.61
MPC		0.59
ClinPred		0.84	D
GERP RS		-3.1
Varity_R		0.20
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr6-42893066;