Variant chr12-54963850-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136030.3(TESPA1):c.547G>T(p.Ala183Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TESPA1
NM_001136030.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.426

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048734188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TESPA1	NM_001136030.3 linkuse as main transcript	c.547G>T	p.Ala183Ser	missense_variant	8/11	ENST00000449076.6	NP_001129502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TESPA1	ENST00000449076.6 linkuse as main transcript	c.547G>T	p.Ala183Ser	missense_variant	8/11	2	NM_001136030.3	ENSP00000400892	P1	A2RU30-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249198

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135188

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000501

Gnomad SAS 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:

0.00000479

AC:

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000414

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.547G>T (p.A183S) alteration is located in exon 8 (coding exon 7) of the TESPA1 gene. This alteration results from a G to T substitution at nucleotide position 547, causing the alanine (A) at amino acid position 183 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0098

.;.;T;T;.;.;.;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.74

.;.;.;T;T;T;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.049

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.77

.;.;N;N;.;.;.;.

MutationTaster

Benign

0.59

N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.85

N;N;N;N;N;N;N;N

REVEL

Benign

0.031

Sift

Benign

0.24

T;T;T;T;T;T;T;T

Sift4G

Benign

0.36

T;T;T;T;.;T;.;.

Polyphen

0.11

.;.;B;B;.;.;.;.

Vest4

0.24

MutPred

0.30

.;.;Gain of disorder (P = 0.0188);Gain of disorder (P = 0.0188);.;.;.;.;

MVP

0.27

MPC

0.41

ClinPred

0.13

GERP RS

4.3

Varity_R

0.045

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over