Variant 1-161038553-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001113207.2(TSTD1):c.131C>T(p.Pro44Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,540,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

TSTD1
NM_001113207.2 missense, splice_region

Scores

Splicing: ADA: 0.9975

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, Cadd, dbscSNV1_ADA, dbscSNV1_RF, Eigen, M_CAP, MutationAssessor, PROVEAN [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster, phyloP100way_vertebrate was below the threshold]

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSTD1	NM_001113207.2 link	c.131C>T	p.Pro44Leu	missense_variant, splice_region_variant	2/4	ENST00000423014.3	NP_001106678.1	Q8NFU3-1
TSTD1	NM_001113205.2 link	c.131C>T	p.Pro44Leu	missense_variant, splice_region_variant	2/3		NP_001106676.1	Q8NFU3-3
TSTD1	NM_001113206.2 link	c.10+327C>T		intron_variant			NP_001106677.1	Q8NFU3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSTD1	ENST00000423014.3 link	c.131C>T	p.Pro44Leu	missense_variant, splice_region_variant	2/4	2	NM_001113207.2	ENSP00000388293.2		Q8NFU3-1
ENSG00000270149	ENST00000289779.7 link	n.10+327C>T		intron_variant		2		ENSP00000289779.4		A0A0A0MQY5

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD3 exomes

AF:

0.0000789

AC:

AN:

152072

Hom.:

AF XY:

0.0000741

AC XY:

AN XY:

80920

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.0000411

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:

0.0000516

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000763

AC:

106

AN:

1388652

Hom.:

Cov.:

AF XY:

0.0000718

AC XY:

AN XY:

682466

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.0000284

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:

0.0000551

Gnomad4 OTH exome

AF:

0.0000523

GnomAD4 genome

AF:

0.000329

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.000131

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:

0.000330

Hom.:

Bravo

AF:

0.000378

ESP6500AA

AF:

0.00217

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000114

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

Nov 13, 2024

The c.131C>T (p.P44L) alteration is located in exon 2 (coding exon 2) of the TSTD1 gene. This alteration results from a C to T substitution at nucleotide position 131, causing the proline (P) at amino acid position 44 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

Pathogenic

0.66

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

.;.;T

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Uncertain

-0.11

MutationAssessor

Pathogenic

4.6

H;.;H

PROVEAN

Pathogenic

-9.3

D;D;D

REVEL

Uncertain

0.48

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.54

MVP

0.48

ClinPred

0.97

GERP RS

4.3

Varity_R

0.88

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.85

SpliceAI score (max)

0.14

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