Variant 1-161038559-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001113207.2(TSTD1):c.125A>G(p.Asn42Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000972 in 1,542,562 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: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

TSTD1
NM_001113207.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSTD1	NM_001113207.2 linkuse as main transcript	c.125A>G	p.Asn42Ser	missense_variant	2/4	ENST00000423014.3	NP_001106678.1	Q8NFU3-1
TSTD1	NM_001113205.2 linkuse as main transcript	c.125A>G	p.Asn42Ser	missense_variant	2/3		NP_001106676.1	Q8NFU3-3
TSTD1	NM_001113206.2 linkuse as main transcript	c.10+321A>G		intron_variant			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.125A>G	p.Asn42Ser	missense_variant	2/4	2	NM_001113207.2	ENSP00000388293.2		Q8NFU3-1
ENSG00000270149	ENST00000289779.7 linkuse as main transcript	n.10+321A>G		intron_variant		2		ENSP00000289779.4		A0A0A0MQY5

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000503

AC:

AN:

1390362

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

683694

show subpopulations

Gnomad4 AFR exome

AF:

0.000159

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:

0.0000348

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000169

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000775

Hom.:

Bravo

AF:

0.0000567

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

Mar 24, 2023

The c.125A>G (p.N42S) alteration is located in exon 2 (coding exon 2) of the TSTD1 gene. This alteration results from a A to G substitution at nucleotide position 125, causing the asparagine (N) at amino acid position 42 to be replaced by a serine (S). 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

0.20

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

.;.;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.053

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

M;.;M

PROVEAN

Uncertain

-4.3

D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.023

D;D;D

Sift4G

Uncertain

0.050

T;D;T

Polyphen

0.86

P;.;D

Vest4

0.50

MVP

0.048

ClinPred

0.99

GERP RS

3.3

Varity_R

0.39

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.22

Position offset: -8

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