Genetic Variant PTCRA:p.Arg187Cys (chr6-42925395-C-T) – ACMG Classification: Likely_benign (-4 pts)

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.23

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

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

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:

AN:

152208

Hom.:

Cov.:

show subpopulations

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:

AN:

155558

AF XY:

0.000349

show subpopulations

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.:

Cov.:

AF XY:

0.000546

AC XY:

378

AN XY:

691910

show subpopulations

African (AFR)

AF:

0.0000945

AC:

AN:

31734

American (AMR)

AF:

0.000111

AC:

AN:

36194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

36018

South Asian (SAS)

AF:

0.00

AC:

AN:

79736

European-Finnish (FIN)

AF:

0.0000205

AC:

AN:

48712

Middle Eastern (MID)

AF:

0.000182

AC:

AN:

5504

European-Non Finnish (NFE)

AF:

0.000723

AC:

781

AN:

1080558

Other (OTH)

AF:

0.000379

AC:

AN:

58080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

105

158

210

263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000400

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41576

American (AMR)

AF:

0.000131

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000706

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000569

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.000238

AC:

ESP6500EA

AF:

0.000368

AC:

ExAC

AF:

0.000209

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.61

M_CAP

Benign

0.058

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

PhyloP100

-2.2

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.8

REVEL

Benign

0.054

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.013

Polyphen

1.0

Vest4

0.12

MVP

0.64

MPC

0.57

ClinPred

0.071

GERP RS

0.33

Varity_R

0.22

gMVP

0.12

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over