rs1801876

Variant names:

• chr12-54950240-G-A
• rs1801876
• NM_001136030.3:c.*152C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-54950240-G-A
• chr12-54950240-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136030.3(TESPA1):​c.*152C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 456,228 control chromosomes in the GnomAD database, including 13,129 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 0.13 (2585 hom., cov: 32)
  • Exomes 𝑓: 0.19 (10544 hom.)
• Consequence: TESPA1 NM_001136030.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.8298).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TESPA1	NM_001136030.3	c.*152C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000449076.6	NP_001129502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TESPA1	ENST00000449076.6	c.*152C>T		3_prime_UTR_variant	Exon 11 of 11	2	NM_001136030.3	ENSP00000400892.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19964 AN: 152036 Hom.: 2580 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0709

Gnomad OTH AF: 0.149

GnomAD2 exomes AF: 0.226 AC: 30867 AN: 136420 AF XY: 0.237

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.241

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.669

Gnomad FIN exome AF: 0.0907

Gnomad NFE exome AF: 0.0738

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.193 AC: 58603 AN: 304074 Hom.: 10544 Cov.: 0 AF XY: 0.217 AC XY: 37575 AN XY: 173160

African (AFR) AF: 0.109 AC: 940 AN: 8598

American (AMR) AF: 0.239 AC: 6506 AN: 27272

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 1984 AN: 10776

East Asian (EAS) AF: 0.661 AC: 6087 AN: 9206

South Asian (SAS) AF: 0.462 AC: 27572 AN: 59688

European-Finnish (FIN) AF: 0.0949 AC: 1233 AN: 12998

Middle Eastern (MID) AF: 0.175 AC: 424 AN: 2420

European-Non Finnish (NFE) AF: 0.0719 AC: 11431 AN: 158920

Other (OTH) AF: 0.171 AC: 2426 AN: 14196

GnomAD4 genome AF: 0.131 AC: 19977 AN: 152154 Hom.: 2585 Cov.: 32 AF XY: 0.142 AC XY: 10562 AN XY: 74366

African (AFR) AF: 0.110 AC: 4547 AN: 41512

American (AMR) AF: 0.189 AC: 2885 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 610 AN: 3466

East Asian (EAS) AF: 0.645 AC: 3319 AN: 5144

South Asian (SAS) AF: 0.491 AC: 2364 AN: 4810

European-Finnish (FIN) AF: 0.0905 AC: 958 AN: 10588

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.0709 AC: 4822 AN: 68024

Other (OTH) AF: 0.155 AC: 327 AN: 2112

Alfa AF: 0.101 Hom.: 5476

Bravo AF: 0.136

TwinsUK AF: 0.0693 AC: 257

ALSPAC AF: 0.0690 AC: 266

ExAC AF: 0.230 AC: 4664

Asia WGS AF: 0.502 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.91
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.025	N
PhyloP100		0.34
GERP RS		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs1801876; hg19: chr12-55344024; COSMIC: COSV57260507; COSMIC: COSV57260507;