rs187988655

Variant names:

• chr6-42925395-C-G
• rs187988655
• NM_138296.3:c.559C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-42925395-C-G
• chr6-42925395-C-T

Variant summary

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

The NM_138296.3(PTCRA):​c.559C>G​(p.Arg187Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000571 in 1,401,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R187C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: PTCRA NM_138296.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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=0.10730812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCRA	NM_138296.3	c.559C>G	p.Arg187Gly	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.559C>G	p.Arg187Gly	missense_variant	Exon 4 of 4	1	NM_138296.3	ENSP00000304447.2
PTCRA	ENST00000441198.4	c.484C>G	p.Arg162Gly	missense_variant	Exon 5 of 5	1		ENSP00000409550.1
PTCRA	ENST00000446507.5	c.238C>G	p.Arg80Gly	missense_variant	Exon 3 of 3	1		ENSP00000392288.1
PTCRA	ENST00000616441.2	c.604C>G	p.Arg202Gly	missense_variant	Exon 4 of 4	2		ENSP00000477815.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000643 AC: 1 AN: 155558 Hom.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 83012

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: 0.0000168

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000571 AC: 8 AN: 1401714 Hom.: 0 Cov.: 32 AF XY: 0.00000867 AC XY: 6 AN XY: 691910

Gnomad4 AFR exome AF: 0.00

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: 0.00000740

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;.;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.53	T;T;T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N;.;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.7	N;N;D;.
REVEL	Benign	0.027
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.0040	B;B;B;.
Vest4		0.090
MutPred		0.25		Loss of helix (P = 0.0167);.;.;.;
MVP		0.46
MPC		0.24
ClinPred		0.16	T
GERP RS		0.33
Varity_R		0.21
gMVP		0.10

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

Other links and lift over

dbSNP: rs187988655; hg19: chr6-42893133;