rs187988655

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138296.3(PTCRA):​c.559C>T​(p.Arg187Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000562 in 1,554,040 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (1 hom.)
• Consequence: PTCRA NM_138296.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.23
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02732271).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138296.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCRA	NM_138296.3	MANE Select	c.559C>T	p.Arg187Cys	missense	Exon 4 of 4	NP_612153.2	Q6ISU1-1
	PTCRA	NM_001243168.2		c.604C>T	p.Arg202Cys	missense	Exon 4 of 4	NP_001230097.1	A0A087WTE9
	PTCRA	NM_001243169.2		c.484C>T	p.Arg162Cys	missense	Exon 5 of 5	NP_001230098.1	Q6ISU1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCRA	ENST00000304672.6	TSL:1 MANE Select	c.559C>T	p.Arg187Cys	missense	Exon 4 of 4	ENSP00000304447.2	Q6ISU1-1
	PTCRA	ENST00000441198.4	TSL:1	c.484C>T	p.Arg162Cys	missense	Exon 5 of 5	ENSP00000409550.1	Q6ISU1-3
	PTCRA	ENST00000446507.5	TSL:1	c.238C>T	p.Arg80Cys	missense	Exon 3 of 3	ENSP00000392288.1	Q6ISU1-2

Frequencies

GnomAD3 genomes AF: 0.000401 AC: 61 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000341 AC: 53 AN: 155558 AF XY: 0.000349

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000657

Gnomad NFE exome AF: 0.000772

Gnomad OTH exome AF: 0.000456

GnomAD4 exome AF: 0.000579 AC: 812 AN: 1401714 Hom.: 1 Cov.: 32 AF XY: 0.000546 AC XY: 378 AN XY: 691910

African (AFR) AF: 0.0000945 AC: 3 AN: 31734

American (AMR) AF: 0.000111 AC: 4 AN: 36194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 36018

South Asian (SAS) AF: 0.00 AC: 0 AN: 79736

European-Finnish (FIN) AF: 0.0000205 AC: 1 AN: 48712

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5504

European-Non Finnish (NFE) AF: 0.000723 AC: 781 AN: 1080558

Other (OTH) AF: 0.000379 AC: 22 AN: 58080

GnomAD4 genome AF: 0.000400 AC: 61 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24 AN XY: 74482

African (AFR) AF: 0.000216 AC: 9 AN: 41576

American (AMR) AF: 0.000131 AC: 2 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000569 Hom.: 0

Bravo AF: 0.000351

ESP6500AA AF: 0.000238 AC: 1

ESP6500EA AF: 0.000368 AC: 3

ExAC AF: 0.000209 AC: 23

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		-2.2
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.054
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.12
MVP		0.64
MPC		0.57
ClinPred		0.071	T
GERP RS		0.33
Varity_R		0.22
gMVP		0.12
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs187988655; hg19: chr6-42893133; COSMIC: COSV100485714; COSMIC: COSV100485714;