12-54950349-C-T

Position:

• chr12-54950349-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136030.3(TESPA1):​c.*43G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081214756).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.49
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.79	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.079
Sift	Pathogenic	0.0	D
MutPred		0.15		Gain of phosphorylation at G95 (P = 0.0408);
MVP		0.014
ClinPred		0.067	T
GERP RS		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;