Variant 1-161037786-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001113207.2(TSTD1):c.337A>G(p.Lys113Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000412 in 1,551,690 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 2 hom. )

Consequence

TSTD1
NM_001113207.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12194154).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSTD1	NM_001113207.2 linkuse as main transcript	c.337A>G	p.Lys113Glu	missense_variant	4/4	ENST00000423014.3	NP_001106678.1	Q8NFU3-1
TSTD1	NM_001113206.2 linkuse as main transcript	c.214A>G	p.Lys72Glu	missense_variant	3/3		NP_001106677.1	Q8NFU3-2
TSTD1	NM_001113205.2 linkuse as main transcript	c.*93A>G		3_prime_UTR_variant	3/3		NP_001106676.1	Q8NFU3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSTD1	ENST00000423014.3 linkuse as main transcript	c.337A>G	p.Lys113Glu	missense_variant	4/4	2	NM_001113207.2	ENSP00000388293.2		Q8NFU3-1
ENSG00000270149	ENST00000289779.7 linkuse as main transcript	n.10+1094A>G		intron_variant		2		ENSP00000289779.4		A0A0A0MQY5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000639

AC:

AN:

156600

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83012

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.0000436

AC:

AN:

1399430

Hom.:

Cov.:

AF XY:

0.0000493

AC XY:

AN XY:

690228

show subpopulations

Gnomad4 AFR exome

AF:

0.000949

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:

0.00000278

Gnomad4 OTH exome

AF:

0.000328

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0000481

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

Alfa

AF:

0.0000882

Hom.:

Bravo

AF:

0.0000302

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jan 10, 2022

The c.337A>G (p.K113E) alteration is located in exon 4 (coding exon 4) of the TSTD1 gene. This alteration results from a A to G substitution at nucleotide position 337, causing the lysine (K) at amino acid position 113 to be replaced by a glutamic acid (E). 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

-0.033

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

.;.;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.49

T;T;T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;.;L;.

PROVEAN

Benign

-1.7

N;N;N;.

REVEL

Benign

0.11

Sift

Uncertain

0.015

D;D;T;.

Sift4G

Benign

0.072

T;D;T;D

Polyphen

0.78, 0.17

.;P;B;.

Vest4

0.33

MutPred

0.53

.;.;Loss of methylation at K113 (P = 0.0041);.;

MVP

0.030

ClinPred

0.12

GERP RS

2.5

Varity_R

0.23

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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