dbSNP rs2171497: TESPA1:c.*43G>T (chr12-54950349-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001136030.3(TESPA1):c.*43G>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 0.00000876 in 456,656 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

TESPA1
NM_001136030.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.578

Publications

11 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08576006).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000729

AC:

AN:

137122

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000985

AC:

AN:

304572

Hom.:

Cov.:

AF XY:

0.00000577

AC XY:

AN XY:

173416

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8626

American (AMR)

AF:

0.00

AC:

AN:

27276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10788

East Asian (EAS)

AF:

0.00

AC:

AN:

9210

South Asian (SAS)

AF:

0.0000502

AC:

AN:

59738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12992

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2774

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

158928

Other (OTH)

AF:

0.00

AC:

AN:

14240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

127

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.45

CADD

Benign

4.9

(source)

DANN

Benign

0.48

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.24

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.87

PhyloP100

0.58

PROVEAN

Benign

-0.83

REVEL

Benign

0.023

Sift

Pathogenic

0.0

MutPred

0.24

Gain of sheet (P = 0.0101)

MVP

0.067

ClinPred

0.053

GERP RS

1.1

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over