Variant 9-97605547-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139246.5(TSTD2):c.1049G>C(p.Arg350Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,878 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: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TSTD2
NM_139246.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

TSTD2 (HGNC:30087): (thiosulfate sulfurtransferase like domain containing 2)

TSTD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.14620653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSTD2	NM_139246.5 linkuse as main transcript	c.1049G>C	p.Arg350Thr	missense_variant	8/10	ENST00000341170.5	NP_640339.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSTD2	ENST00000341170.5 linkuse as main transcript	c.1049G>C	p.Arg350Thr	missense_variant	8/10	1	NM_139246.5	ENSP00000342499	P1	Q5T7W7-1
TSTD2	ENST00000375165.5 linkuse as main transcript	c.*729G>C		3_prime_UTR_variant, NMD_transcript_variant	5/6	1		ENSP00000364308
TSTD2	ENST00000375172.6 linkuse as main transcript	c.*961G>C		3_prime_UTR_variant, NMD_transcript_variant	8/10	5		ENSP00000364315

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251476

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135920

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:

0.0000462

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727238

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:

0.0000374

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 10, 2022

The c.1049G>C (p.R350T) alteration is located in exon 8 (coding exon 7) of the TSTD2 gene. This alteration results from a G to C substitution at nucleotide position 1049, causing the arginine (R) at amino acid position 350 to be replaced by a threonine (T). 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

0.085

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.011

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.71

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.78

M_CAP

Benign

0.0060

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.30

MutationTaster

Benign

0.95

N;N;N;N

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-2.1

REVEL

Benign

0.068

Sift

Benign

0.17

Sift4G

Benign

0.25

Polyphen

0.0070

Vest4

0.30

MutPred

0.64

Loss of ubiquitination at K349 (P = 0.0593);

MVP

0.10

MPC

0.058

ClinPred

0.036

GERP RS

-0.091

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.071

gMVP

0.65

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