Variant 3-150409667-G-T 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.317G>T(p.Gly106Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,598,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

TSC22D2
NM_001303264.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

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=0.086250424).

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC22D2	NM_001303264.2 linkuse as main transcript	c.317G>T	p.Gly106Val	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.317G>T	p.Gly106Val	missense_variant	1/3		NM_001303264.2	ENSP00000510392	A2	O75157-2
TSC22D2	ENST00000361875.8 linkuse as main transcript	c.317G>T	p.Gly106Val	missense_variant	1/4	1		ENSP00000354543	P2	O75157-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000107

AC:

AN:

214218

Hom.:

AF XY:

0.0000508

AC XY:

AN XY:

118198

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000600

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:

0.0000323

Gnomad OTH exome

AF:

0.000184

GnomAD4 exome

AF:

0.0000595

AC:

AN:

1446228

Hom.:

Cov.:

AF XY:

0.0000487

AC XY:

AN XY:

717986

show subpopulations

Gnomad4 AFR exome

AF:

0.0000602

Gnomad4 AMR exome

AF:

0.000537

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:

0.0000516

Gnomad4 OTH exome

AF:

0.0000669

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000178

ExAC

AF:

0.0000667

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

Sep 06, 2022

The c.317G>T (p.G106V) alteration is located in exon 1 (coding exon 1) of the TSC22D2 gene. This alteration results from a G to T substitution at nucleotide position 317, causing the glycine (G) at amino acid position 106 to be replaced by a valine (V). 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

0.089

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0093

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.63

M_CAP

Benign

0.017

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.6

REVEL

Benign

0.11

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.046

Polyphen

0.77

Vest4

0.28

MVP

0.068

ClinPred

0.089

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.18

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