chr3-150409687-G-T

Position:

• chr3-150409687-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001303264.2(TSC22D2):​c.337G>T​(p.Val113Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 7.0e-7 (0 hom.)
• Consequence: TSC22D2 NM_001303264.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.634

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07583243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC22D2	NM_001303264.2	c.337G>T	p.Val113Leu	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	c.337G>T	p.Val113Leu	missense_variant	1/3		NM_001303264.2	ENSP00000510392	A2
TSC22D2	ENST00000361875.8	c.337G>T	p.Val113Leu	missense_variant	1/4	1		ENSP00000354543	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436602 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 712628

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: 0.0000216

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.337G>T (p.V113L) 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 337, causing the valine (V) at amino acid position 113 to be replaced by a leucine (L). 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	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.031
Sift	Uncertain	0.023	D
Sift4G	Benign	0.35	T
Polyphen		0.011	B
Vest4		0.25
MutPred		0.28		Loss of sheet (P = 0.0457);
MVP		0.043
ClinPred		0.073	T
GERP RS		3.6
Varity_R		0.13
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-150127474;