NM_138296.3:c.527C>T

Variant names:

• chr6-42925363-C-T
• rs376897338
• NM_138296.3:c.527C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138296.3(PTCRA):​c.527C>T​(p.Ala176Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000569 in 1,405,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A176E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: PTCRA NM_138296.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07681945).

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.527C>T	p.Ala176Val	missense	Exon 4 of 4	NP_612153.2	Q6ISU1-1
	PTCRA	NM_001243168.2		c.572C>T	p.Ala191Val	missense	Exon 4 of 4	NP_001230097.1	A0A087WTE9
	PTCRA	NM_001243169.2		c.452C>T	p.Ala151Val	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.527C>T	p.Ala176Val	missense	Exon 4 of 4	ENSP00000304447.2	Q6ISU1-1
	PTCRA	ENST00000441198.4	TSL:1	c.452C>T	p.Ala151Val	missense	Exon 5 of 5	ENSP00000409550.1	Q6ISU1-3
	PTCRA	ENST00000446507.5	TSL:1	c.206C>T	p.Ala69Val	missense	Exon 3 of 3	ENSP00000392288.1	Q6ISU1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000125 AC: 2 AN: 159380 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 8 AN: 1405894 Hom.: 0 Cov.: 32 AF XY: 0.00000288 AC XY: 2 AN XY: 694934

African (AFR) AF: 0.000125 AC: 4 AN: 32078

American (AMR) AF: 0.00 AC: 0 AN: 37148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25246

East Asian (EAS) AF: 0.00 AC: 0 AN: 36652

South Asian (SAS) AF: 0.00 AC: 0 AN: 80436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46566

Middle Eastern (MID) AF: 0.000188 AC: 1 AN: 5316

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1084192

Other (OTH) AF: 0.0000172 AC: 1 AN: 58260

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.040
DANN	Benign	0.82
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.74
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.27
Sift	Benign	0.051	T
Sift4G	Benign	0.15	T
Polyphen		0.025	B
Vest4		0.076
MutPred		0.23		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.061
MPC		0.15
ClinPred		0.071	T
GERP RS		-4.5
Varity_R		0.039
gMVP		0.10
Mutation Taster		=100/0	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: rs376897338; hg19: chr6-42893101;