Variant 1-161037821-C-T 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_001113207.2(TSTD1):c.302G>A(p.Arg101His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,551,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

TSTD1
NM_001113207.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

Variant links:

Genes affected

TSTD1 (HGNC:35410): (thiosulfate sulfurtransferase like domain containing 1) Predicted to enable thiosulfate-thiol sulfurtransferase activity. Predicted to be involved in sulfide oxidation, using sulfide:quinone oxidoreductase. Located in cytoplasmic ribonucleoprotein granule and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TSTD1 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=0.11385214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TSTD1	NM_001113207.2 linkuse as main transcript	c.302G>A	p.Arg101His	missense_variant	4/4	ENST00000423014.3	NP_001106678.1
TSTD1	NM_001113206.2 linkuse as main transcript	c.179G>A	p.Arg60His	missense_variant	3/3		NP_001106677.1
TSTD1	NM_001113205.2 linkuse as main transcript	c.*58G>A		3_prime_UTR_variant	3/3		NP_001106676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSTD1	ENST00000423014.3 linkuse as main transcript	c.302G>A	p.Arg101His	missense_variant	4/4	2	NM_001113207.2	ENSP00000388293	A2	Q8NFU3-1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000575

AC:

AN:

156636

Hom.:

AF XY:

0.0000482

AC XY:

AN XY:

83032

show subpopulations

Gnomad AFR exome

AF:

0.000505

Gnomad AMR exome

AF:

0.0000405

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:

0.0000495

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.0000886

AC:

124

AN:

1399444

Hom.:

Cov.:

AF XY:

0.0000956

AC XY:

AN XY:

690234

show subpopulations

Gnomad4 AFR exome

AF:

0.000886

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000658

Gnomad4 OTH exome

AF:

0.000190

GnomAD4 genome

AF:

0.000269

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000844

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000172

Hom.:

Bravo

AF:

0.000306

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000743

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

Aug 17, 2022

The c.302G>A (p.R101H) alteration is located in exon 4 (coding exon 4) of the TSTD1 gene. This alteration results from a G to A substitution at nucleotide position 302, causing the arginine (R) at amino acid position 101 to be replaced by a histidine (H). 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

0.18

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

.;.;T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;.;L;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PROVEAN

Uncertain

-3.1

D;D;D;.

REVEL

Benign

0.075

Sift

Uncertain

0.0050

D;D;D;.

Sift4G

Benign

0.11

T;T;T;D

Polyphen

0.53, 0.016

.;P;B;.

Vest4

0.21

MVP

0.030

ClinPred

0.14

GERP RS

3.2

Varity_R

0.39

gMVP

0.52

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