6-42925267-C-A

Variant names:

• chr6-42925267-C-A
• rs564467179
• NM_138296.3:c.431C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138296.3(PTCRA):​c.431C>A​(p.Pro144Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 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. P144L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PTCRA NM_138296.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06119576).

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.431C>A	p.Pro144Gln	missense	Exon 4 of 4	NP_612153.2	Q6ISU1-1
	PTCRA	NM_001243168.2		c.476C>A	p.Pro159Gln	missense	Exon 4 of 4	NP_001230097.1	A0A087WTE9
	PTCRA	NM_001243169.2		c.356C>A	p.Pro119Gln	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.431C>A	p.Pro144Gln	missense	Exon 4 of 4	ENSP00000304447.2	Q6ISU1-1
	PTCRA	ENST00000441198.4	TSL:1	c.356C>A	p.Pro119Gln	missense	Exon 5 of 5	ENSP00000409550.1	Q6ISU1-3
	PTCRA	ENST00000446507.5	TSL:1	c.110C>A	p.Pro37Gln	missense	Exon 3 of 3	ENSP00000392288.1	Q6ISU1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436058 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 713792

African (AFR) AF: 0.00 AC: 0 AN: 33294

American (AMR) AF: 0.00 AC: 0 AN: 43314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25768

East Asian (EAS) AF: 0.00 AC: 0 AN: 39294

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106676

Other (OTH) AF: 0.00 AC: 0 AN: 59734

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.0
DANN	Benign	0.92
DEOGEN2	Benign	0.078	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.3
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.023
Sift	Benign	0.12	T
Sift4G	Benign	0.38	T
Polyphen		0.062	B
Vest4		0.15
MutPred		0.20		Loss of glycosylation at P144 (P = 0.0504)
MVP		0.085
MPC		0.34
ClinPred		0.075	T
GERP RS		-7.1
Varity_R		0.022
gMVP		0.13
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 2

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

Other links and lift over

dbSNP: rs564467179; hg19: chr6-42893005;