Variant 1-161037931-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001113207.2(TSTD1):c.278G>T(p.Arg93Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,551,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TSTD1
NM_001113207.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.27

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:

ENSG00000270149 (HGNC:):

ENSG00000270149 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043218344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSTD1	NM_001113207.2 linkuse as main transcript	c.278G>T	p.Arg93Leu	missense_variant	3/4	ENST00000423014.3	NP_001106678.1	Q8NFU3-1
TSTD1	NM_001113205.2 linkuse as main transcript	c.278G>T	p.Arg93Leu	missense_variant	3/3		NP_001106676.1	Q8NFU3-3
TSTD1	NM_001113206.2 linkuse as main transcript	c.155G>T	p.Arg52Leu	missense_variant	2/3		NP_001106677.1	Q8NFU3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSTD1	ENST00000423014.3 linkuse as main transcript	c.278G>T	p.Arg93Leu	missense_variant	3/4	2	NM_001113207.2	ENSP00000388293.2		Q8NFU3-1
ENSG00000270149	ENST00000289779.7 linkuse as main transcript	n.10+949G>T		intron_variant		2		ENSP00000289779.4		A0A0A0MQY5

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000637

AC:

AN:

156866

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83106

show subpopulations

Gnomad AFR exome

AF:

0.000125

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1399508

Hom.:

Cov.:

AF XY:

0.00000724

AC XY:

AN XY:

690260

show subpopulations

Gnomad4 AFR exome

AF:

0.000411

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.000105

AC:

AN:

152374

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000385

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000102

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

Oct 05, 2023

The c.278G>T (p.R93L) alteration is located in exon 3 (coding exon 3) of the TSTD1 gene. This alteration results from a G to T substitution at nucleotide position 278, causing the arginine (R) at amino acid position 93 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

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.20

DANN

Benign

0.76

DEOGEN2

Benign

0.039

.;.;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.66

T;T;T;T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.043

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.25

N;.;.;N;.

PROVEAN

Uncertain

-2.8

D;N;D;N;.

REVEL

Benign

0.029

Sift

Benign

0.68

T;T;T;T;.

Sift4G

Benign

0.37

T;T;D;T;T

Polyphen

0.041

B;.;B;B;.

Vest4

0.15

MutPred

0.52

Loss of MoRF binding (P = 0.0082);.;.;Loss of MoRF binding (P = 0.0082);.;

MVP

0.030

ClinPred

0.014

GERP RS

-3.7

Varity_R

0.29

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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