Variant 3-150409742-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001303264.2(TSC22D2):c.392C>G(p.Pro131Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,449,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TSC22D2
NM_001303264.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.197

Variant links:

Genes affected

TSC22D2 (HGNC:29095): (TSC22 domain family member 2) Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within response to osmotic stress. [provided by Alliance of Genome Resources, Apr 2022]

TSC22D2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.072117).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC22D2	NM_001303264.2 linkuse as main transcript	c.392C>G	p.Pro131Arg	missense_variant	1/3	ENST00000688009.1	NP_001290193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSC22D2	ENST00000688009.1 linkuse as main transcript	c.392C>G	p.Pro131Arg	missense_variant	1/3		NM_001303264.2	ENSP00000510392	A2	O75157-2
TSC22D2	ENST00000361875.8 linkuse as main transcript	c.392C>G	p.Pro131Arg	missense_variant	1/4	1		ENSP00000354543	P2	O75157-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000869

AC:

AN:

230146

Hom.:

AF XY:

0.0000157

AC XY:

AN XY:

127480

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000193

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000483

AC:

AN:

1449120

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

720692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000853

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Feb 21, 2024

The c.392C>G (p.P131R) alteration is located in exon 1 (coding exon 1) of the TSC22D2 gene. This alteration results from a C to G substitution at nucleotide position 392, causing the proline (P) at amino acid position 131 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.56

M_CAP

Benign

0.0072

MetaRNN

Benign

0.072

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.8

REVEL

Benign

0.055

Sift

Benign

0.030

Sift4G

Benign

0.14

Polyphen

0.0040

Vest4

0.11

MutPred

0.28

Gain of methylation at P131 (P = 0.0025);

MVP

0.043

ClinPred

0.039

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.072

gMVP

0.27

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