Variant 22-37011233-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003312.6(TST):c.688C>T(p.Arg230Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,732 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R230H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TST
NM_003312.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

Variant links:

Genes affected

TST (HGNC:12388): (thiosulfate sulfurtransferase) This is one of two neighboring genes encoding similar proteins that each contain two rhodanese domains. The encoded protein is localized to the mitochondria and catalyzes the conversion of thiosulfate and cyanide to thiocyanate and sulfite. In addition, the protein interacts with 5S ribosomal RNA and facilitates its import into the mitochondria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

TST links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41673237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TST	NM_003312.6 linkuse as main transcript	c.688C>T	p.Arg230Cys	missense_variant	3/3	ENST00000249042.8
TST	NM_001270483.1 linkuse as main transcript	c.688C>T	p.Arg230Cys	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TST	ENST00000249042.8 linkuse as main transcript	c.688C>T	p.Arg230Cys	missense_variant	3/3	1	NM_003312.6	P1
TST	ENST00000403892.7 linkuse as main transcript	c.688C>T	p.Arg230Cys	missense_variant	2/2	1		P1
TST	ENST00000622841.1 linkuse as main transcript	c.688C>T	p.Arg230Cys	missense_variant	3/3	5		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251234

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461732

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000277

Hom.:

ExAC

AF:

0.0000741

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;T;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.027

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Pathogenic

3.2

M;M;M

MutationTaster

Benign

0.87

N;N

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-5.2

D;D;.

REVEL

Benign

0.19

Sift

Uncertain

0.0030

D;D;.

Sift4G

Uncertain

0.021

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.14

MutPred

0.61

Loss of disorder (P = 0.0272);Loss of disorder (P = 0.0272);Loss of disorder (P = 0.0272);

MVP

0.44

MPC

0.59

ClinPred

0.67

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.23

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over