Variant 12-117049125-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017899.4(TESC):c.243T>G(p.Asp81Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000592 in 152,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TESC
NM_017899.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.42

Variant links:

Genes affected

TESC (HGNC:26065): (tescalcin) Enables calcium ion binding activity. Involved in several processes, including cellular response to retinoic acid; positive regulation of macromolecule metabolic process; and positive regulation of myeloid cell differentiation. Located in several cellular components, including cytosol; lamellipodium; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TESC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044602215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TESC	NM_017899.4 link	c.243T>G	p.Asp81Glu	missense_variant	4/8	ENST00000335209.12	NP_060369.3	Q96BS2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TESC	ENST00000335209.12 link	c.243T>G	p.Asp81Glu	missense_variant	4/8	1	NM_017899.4	ENSP00000334785.7		Q96BS2-1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151926

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000950

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251456

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00325

AC:

4615

AN:

1419868

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

2137

AN XY:

707546

show subpopulations

Gnomad4 AFR exome

AF:

0.00297

Gnomad4 AMR exome

AF:

0.000315

Gnomad4 ASJ exome

AF:

0.00195

Gnomad4 EAS exome

AF:

0.00139

Gnomad4 SAS exome

AF:

0.00106

Gnomad4 FIN exome

AF:

0.00107

Gnomad4 NFE exome

AF:

0.00378

Gnomad4 OTH exome

AF:

0.00294

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000950

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 09, 2022

The c.243T>G (p.D81E) alteration is located in exon 4 (coding exon 4) of the TESC gene. This alteration results from a T to G substitution at nucleotide position 243, causing the aspartic acid (D) at amino acid position 81 to be replaced by a glutamic acid (E). 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

0.075

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.39

DANN

Uncertain

0.98

DEOGEN2

Benign

0.066

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.13

N;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.024

Sift

Benign

0.33

T;T

Sift4G

Benign

0.86

T;T

Polyphen

0.0010

B;.

Vest4

0.29

MutPred

0.48

Gain of catalytic residue at D81 (P = 0.045);.;

MVP

0.23

MPC

0.43

ClinPred

0.026

GERP RS

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.036

gMVP

0.39

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