12-54974461-G-A

Position:

• chr12-54974461-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001136030.3(TESPA1):​c.102C>T​(p.Ala34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,607,252 control chromosomes in the GnomAD database, including 59,339 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 0.25 (5875 hom., cov: 32)
  • Exomes 𝑓: 0.24 (53464 hom.)
• Consequence: TESPA1 NM_001136030.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-2.79 with no splicing effect.
• 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.102C>T	p.Ala34=	synonymous_variant	2/11	ENST00000449076.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TESPA1	ENST00000449076.6	c.102C>T	p.Ala34=	synonymous_variant	2/11	2	NM_001136030.3	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38343 AN: 151976 Hom.: 5866 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.299

GnomAD3 exomes AF: 0.302 AC: 71310 AN: 235928 Hom.: 13994 AF XY: 0.312 AC XY: 39934 AN XY: 128122

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.258

Gnomad ASJ exome AF: 0.383

Gnomad EAS exome AF: 0.718

Gnomad SAS exome AF: 0.547

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.243 AC: 354092 AN: 1455158 Hom.: 53464 Cov.: 33 AF XY: 0.253 AC XY: 182626 AN XY: 723244

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.713

Gnomad4 SAS exome AF: 0.541

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.252 AC: 38360 AN: 152094 Hom.: 5875 Cov.: 32 AF XY: 0.263 AC XY: 19542 AN XY: 74342

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.265

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: 0.305

Alfa AF: 0.225 Hom.: 2274

Bravo AF: 0.255

Asia WGS AF: 0.591 AC: 2056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.8
DANN	Benign	0.69

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: rs4758993; hg19: chr12-55368245; COSMIC: COSV57258059; COSMIC: COSV57258059;