Genetic Variant PTCRA:p.Ala176Glu (chr6-42925363-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138296.3(PTCRA):c.527C>A(p.Ala176Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000642 in 1,558,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

PTCRA
NM_138296.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.742

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017520785).

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.527C>A	p.Ala176Glu	missense	Exon 4 of 4	NP_612153.2	Q6ISU1-1
PTCRA	NM_001243168.2		c.572C>A	p.Ala191Glu	missense	Exon 4 of 4	NP_001230097.1	A0A087WTE9
PTCRA	NM_001243169.2		c.452C>A	p.Ala151Glu	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.527C>A	p.Ala176Glu	missense	Exon 4 of 4	ENSP00000304447.2	Q6ISU1-1
PTCRA	ENST00000441198.4	TSL:1	c.452C>A	p.Ala151Glu	missense	Exon 5 of 5	ENSP00000409550.1	Q6ISU1-3
PTCRA	ENST00000446507.5	TSL:1	c.206C>A	p.Ala69Glu	missense	Exon 3 of 3	ENSP00000392288.1	Q6ISU1-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000188

AC:

AN:

159380

AF XY:

0.0000116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000388

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000160

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.00000569

AC:

AN:

1405896

Hom.:

Cov.:

AF XY:

0.00000576

AC XY:

AN XY:

694936

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32078

American (AMR)

AF:

0.0000538

AC:

AN:

37148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25246

East Asian (EAS)

AF:

0.00

AC:

AN:

36652

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5316

European-Non Finnish (NFE)

AF:

0.00000461

AC:

AN:

1084192

Other (OTH)

AF:

0.00

AC:

AN:

58260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41572

American (AMR)

AF:

0.0000653

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

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:

0.00

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000234

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000175

AC:

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

0.085

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.012

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.12

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.34

M_CAP

Benign

0.021

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

PhyloP100

-0.74

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.87

REVEL

Benign

0.26

Sift

Benign

0.39

Sift4G

Benign

0.53

Polyphen

0.0

Vest4

0.099

MVP

0.11

MPC

0.16

ClinPred

0.062

GERP RS

-4.5

Varity_R

0.11

gMVP

0.095

Mutation Taster

=100/0

polymorphism

(source)

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

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