3-150409423-A-G

Position:

• chr3-150409423-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001303264.2(TSC22D2):​c.73A>G​(p.Ser25Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TSC22D2 NM_001303264.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29146796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC22D2	NM_001303264.2	c.73A>G	p.Ser25Gly	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.73A>G	p.Ser25Gly	missense_variant	1/3		NM_001303264.2	ENSP00000510392	A2
TSC22D2	ENST00000361875.8	c.73A>G	p.Ser25Gly	missense_variant	1/4	1		ENSP00000354543	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461042 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726702

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Aug 29, 2023

The c.73A>G (p.S25G) alteration is located in exon 1 (coding exon 1) of the TSC22D2 gene. This alteration results from a A to G substitution at nucleotide position 73, causing the serine (S) at amino acid position 25 to be replaced by a glycine (G). 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	0.21
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.058
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.24	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	0.69	N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.082
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.20	T
Polyphen		0.12	B
Vest4		0.58
MutPred		0.28		Loss of glycosylation at S25 (P = 0.0118);
MVP		0.043
ClinPred		0.84	D
GERP RS		4.5
Varity_R		0.32
gMVP		0.13

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

Other links and lift over

dbSNP: rs1719409469; hg19: chr3-150127210;