rs4758994

chr12-54974584-G-Achr12-54974584-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136030.3(TESPA1):c.-22C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,529,172 control chromosomes in the GnomAD database, including 57,977 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (7336 hom., cov: 32)
  • Exomes 𝑓: 0.24 (50641 hom.)
• Consequence: TESPA1 NM_001136030.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

Genes affected

TESPA1 (HGNC:29109): (thymocyte expressed, positive selection associated 1) Predicted to enable phospholipase binding activity. Predicted to be involved in several processes, including COP9 signalosome assembly; positive regulation of T cell differentiation in thymus; and positive regulation of T cell receptor signaling pathway. Predicted to act upstream of or within TCR signalosome assembly. Part of COP9 signalosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TESPA1	NM_001136030.3	c.-22C>T		5_prime_UTR_variant	2/11	ENST00000449076.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TESPA1	ENST00000449076.6	c.-22C>T		5_prime_UTR_variant	2/11	2	NM_001136030.3	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43234 AN: 151918 Hom.: 7329 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.327

GnomAD3 exomes AF: 0.314 AC: 49149 AN: 156522 Hom.: 9779 AF XY: 0.322 AC XY: 27031 AN XY: 84072

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.278

Gnomad ASJ exome AF: 0.393

Gnomad EAS exome AF: 0.715

Gnomad SAS exome AF: 0.556

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.244 AC: 336067 AN: 1377136 Hom.: 50641 Cov.: 32 AF XY: 0.252 AC XY: 171107 AN XY: 677674

Gnomad4 AFR exome AF: 0.360

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.711

Gnomad4 SAS exome AF: 0.542

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.290

GnomAD4 genome AF: 0.284 AC: 43252 AN: 152036 Hom.: 7336 Cov.: 32 AF XY: 0.294 AC XY: 21877 AN XY: 74332

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.333

Alfa AF: 0.243 Hom.: 1867

Bravo AF: 0.292

Asia WGS AF: 0.595 AC: 2071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	8.6
Dann	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs4758994; hg19: chr12-55368368;