12-54974584-G-A

Variant names:

• chr12-54974584-G-A
• rs4758994
• NM_001136030.3:c.-22C>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.-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
• Publications: 13 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_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136030.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESPA1	NM_001136030.3	MANE Select	c.-22C>T		5_prime_UTR	Exon 2 of 11	NP_001129502.1	A2RU30-1
	TESPA1	NM_001098815.3		c.-22C>T		5_prime_UTR	Exon 2 of 11	NP_001092285.1	A2RU30-1
	TESPA1	NM_001351149.2		c.-22C>T		5_prime_UTR	Exon 3 of 12	NP_001338078.1	A2RU30-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESPA1	ENST00000449076.6	TSL:2 MANE Select	c.-22C>T		5_prime_UTR	Exon 2 of 11	ENSP00000400892.1	A2RU30-1
	TESPA1	ENST00000316577.12	TSL:1	c.-22C>T		5_prime_UTR	Exon 2 of 11	ENSP00000312679.8	A2RU30-1
	TESPA1	ENST00000868657.1		c.-22C>T		5_prime_UTR	Exon 3 of 12	ENSP00000538716.1

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

GnomAD2 exomes AF: 0.314 AC: 49149 AN: 156522 AF XY: 0.322

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 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

African (AFR) AF: 0.360 AC: 11134 AN: 30906

American (AMR) AF: 0.269 AC: 8677 AN: 32306

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 8745 AN: 23020

East Asian (EAS) AF: 0.711 AC: 26029 AN: 36626

South Asian (SAS) AF: 0.542 AC: 40627 AN: 74972

European-Finnish (FIN) AF: 0.198 AC: 9873 AN: 49790

Middle Eastern (MID) AF: 0.368 AC: 2022 AN: 5498

European-Non Finnish (NFE) AF: 0.199 AC: 212534 AN: 1067444

Other (OTH) AF: 0.290 AC: 16426 AN: 56574

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

African (AFR) AF: 0.353 AC: 14614 AN: 41450

American (AMR) AF: 0.281 AC: 4285 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1350 AN: 3472

East Asian (EAS) AF: 0.706 AC: 3641 AN: 5156

South Asian (SAS) AF: 0.563 AC: 2719 AN: 4826

European-Finnish (FIN) AF: 0.188 AC: 1987 AN: 10576

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.201 AC: 13690 AN: 67966

Other (OTH) AF: 0.333 AC: 703 AN: 2110

Alfa AF: 0.243 Hom.: 2265

Bravo AF: 0.292

Asia WGS AF: 0.595 AC: 2071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.6
DANN	Benign	0.81
PhyloP100		0.56
Mutation Taster		=300/0	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: rs4758994; hg19: chr12-55368368; COSMIC: COSV107344311; COSMIC: COSV107344311;