Genetic Variant PTCRA:p.Asp51Ala (chr6-42923120-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_138296.3(PTCRA):c.152A>C(p.Asp51Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00114 in 1,614,188 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 38 hom. )

Consequence

PTCRA
NM_138296.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.17

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006799668).

BP6

Variant 6-42923120-A-C is Benign according to our data. Variant chr6-42923120-A-C is described in ClinVar as Benign. ClinVar VariationId is 3338637.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00121 (1771/1461892) while in subpopulation SAS AF = 0.0171 (1477/86258). AF 95% confidence interval is 0.0164. There are 38 homozygotes in GnomAdExome4. There are 1269 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 38 AR gene

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.152A>C	p.Asp51Ala	missense	Exon 2 of 4	NP_612153.2	Q6ISU1-1
PTCRA	NM_001243168.2		c.152A>C	p.Asp51Ala	missense	Exon 2 of 4	NP_001230097.1	A0A087WTE9
PTCRA	NM_001243169.2		c.102-25A>C		intron	N/A	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.152A>C	p.Asp51Ala	missense	Exon 2 of 4	ENSP00000304447.2	Q6ISU1-1
PTCRA	ENST00000441198.4	TSL:1	c.102-25A>C		intron	N/A	ENSP00000409550.1	Q6ISU1-3
PTCRA	ENST00000446507.5	TSL:1	c.59-1109A>C		intron	N/A	ENSP00000392288.1	Q6ISU1-2

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00224

AC:

564

AN:

251392

AF XY:

0.00327

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00121

AC:

1771

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1269

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000880

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0171

AC:

1477

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00555

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000118

AC:

131

AN:

1112010

Other (OTH)

AF:

0.00171

AC:

103

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

140

280

419

559

699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.000427

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41556

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0101

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.000616

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00241

AC:

293

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PTCRA POLYMORPHISM (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

Eigen

Benign

0.0069

Eigen_PC

Benign

0.00046

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.9

PhyloP100

5.2

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-6.4

REVEL

Benign

0.24

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.55

MVP

0.72

MPC

0.68

ClinPred

0.13

GERP RS

5.8

La Branchor

0.87

Varity_R

0.53

gMVP

0.61

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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