chr12-54950349-C-G

Position:

• chr12-54950349-C-G

Variant summary

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

The NM_001136030.3(TESPA1):​c.*43G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 456,700 control chromosomes in the GnomAD database, including 12,828 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 0.11 (2350 hom., cov: 32)
  • Exomes 𝑓: 0.19 (10478 hom.)
• Consequence: TESPA1 NM_001136030.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578

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]

TESPA1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.3282156E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TESPA1	NM_001136030.3	c.*43G>C		3_prime_UTR_variant	11/11	ENST00000449076.6	NP_001129502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TESPA1	ENST00000449076.6	c.*43G>C		3_prime_UTR_variant	11/11	2	NM_001136030.3	ENSP00000400892.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17195 AN: 152068 Hom.: 2344 Cov.: 32

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.0908

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0706

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.222 AC: 30434 AN: 137122 Hom.: 6047 AF XY: 0.233 AC XY: 17395 AN XY: 74504

Gnomad AFR exome AF: 0.0447

Gnomad AMR exome AF: 0.238

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.669

Gnomad SAS exome AF: 0.466

Gnomad FIN exome AF: 0.0926

Gnomad NFE exome AF: 0.0736

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.190 AC: 57936 AN: 304516 Hom.: 10478 Cov.: 0 AF XY: 0.215 AC XY: 37314 AN XY: 173384

Gnomad4 AFR exome AF: 0.0439

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.661

Gnomad4 SAS exome AF: 0.462

Gnomad4 FIN exome AF: 0.0951

Gnomad4 NFE exome AF: 0.0717

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.113 AC: 17200 AN: 152184 Hom.: 2350 Cov.: 32 AF XY: 0.124 AC XY: 9250 AN XY: 74386

Gnomad4 AFR AF: 0.0466

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.0908

Gnomad4 NFE AF: 0.0706

Gnomad4 OTH AF: 0.141

Alfa AF: 0.0636 Hom.: 127

Bravo AF: 0.115

TwinsUK AF: 0.0693 AC: 257

ALSPAC AF: 0.0690 AC: 266

ExAC AF: 0.238 AC: 4580

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	3.8
DANN	Benign	0.26
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0000053	T
MetaSVM	Benign	-0.95	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.042
Sift	Pathogenic	0.0	D
ClinPred		0.011	T
GERP RS		1.1

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: rs2171497; hg19: chr12-55344133; COSMIC: COSV57259072; COSMIC: COSV57259072;