12-54950349-C-G

Variant names:

• chr12-54950349-C-G
• rs2171497
• NM_001136030.3:c.*43G>C

Variant summary

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

The ENST00000449076.6(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 ENST00000449076.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578
• Publications: 11 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 (MetaRNN=5.3282156E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000449076.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESPA1	NM_001136030.3	MANE Select	c.*43G>C		3_prime_UTR	Exon 11 of 11	NP_001129502.1
	TESPA1	NR_147062.2		n.2059G>C		non_coding_transcript_exon	Exon 13 of 13
	TESPA1	NR_147063.2		n.1886G>C		non_coding_transcript_exon	Exon 12 of 12

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESPA1	ENST00000449076.6	TSL:2 MANE Select	c.*43G>C		3_prime_UTR	Exon 11 of 11	ENSP00000400892.1
	TESPA1	ENST00000316577.12	TSL:1	c.*43G>C		3_prime_UTR	Exon 11 of 11	ENSP00000312679.8
	TESPA1	ENST00000524622.5	TSL:1	c.*43G>C		3_prime_UTR	Exon 9 of 9	ENSP00000435622.1

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

GnomAD2 exomes AF: 0.222 AC: 30434 AN: 137122 AF XY: 0.233

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 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

African (AFR) AF: 0.0439 AC: 379 AN: 8626

American (AMR) AF: 0.235 AC: 6419 AN: 27272

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 1989 AN: 10788

East Asian (EAS) AF: 0.661 AC: 6085 AN: 9206

South Asian (SAS) AF: 0.462 AC: 27575 AN: 59718

European-Finnish (FIN) AF: 0.0951 AC: 1235 AN: 12988

Middle Eastern (MID) AF: 0.174 AC: 481 AN: 2766

European-Non Finnish (NFE) AF: 0.0717 AC: 11396 AN: 158912

Other (OTH) AF: 0.167 AC: 2377 AN: 14240

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

African (AFR) AF: 0.0466 AC: 1936 AN: 41544

American (AMR) AF: 0.181 AC: 2773 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 610 AN: 3472

East Asian (EAS) AF: 0.645 AC: 3315 AN: 5142

South Asian (SAS) AF: 0.491 AC: 2366 AN: 4818

European-Finnish (FIN) AF: 0.0908 AC: 962 AN: 10592

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.0706 AC: 4800 AN: 68010

Other (OTH) AF: 0.141 AC: 298 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
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
PhyloP100		0.58
PROVEAN	Benign	2.2	N
REVEL	Benign	0.042
Sift	Pathogenic	0.0	D
ClinPred		0.011	T
GERP RS		1.1
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: rs2171497; hg19: chr12-55344133; COSMIC: COSV57259072; COSMIC: COSV57259072;