Variant 22-37024646-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_021126.8(MPST):c.491C>A(p.Ser164Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,598,420 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

MPST
NM_021126.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

Variant links:

Genes affected

MPST (HGNC:7223): (mercaptopyruvate sulfurtransferase) This protein encoded by this gene catalyzes the transfer of a sulfur ion from 3-mercaptopyruvate to cyanide or other thiol compounds. It may be involved in cysteine degradation and cyanide detoxification. There is confusion in literature between this protein (mercaptopyruvate sulfurtransferase, MPST), which appears to be cytoplasmic, and thiosulfate sulfurtransferase (rhodanese, TST, GeneID:7263), which is a mitochondrial protein. Deficiency in MPST activity has been implicated in a rare inheritable disorder known as mercaptolactate-cysteine disulfiduria (MCDU). Alternatively spliced transcript variants encoding same or different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

MPST links:

MPST (HGNC:):

MPST links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a modified_residue N6-succinyllysine (size 0) in uniprot entity THTM_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPST	NM_021126.8 linkuse as main transcript	c.491C>A	p.Ser164Tyr	missense_variant	2/3	ENST00000429360.6	NP_066949.2	P25325-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPST	ENST00000429360.6 linkuse as main transcript	c.491C>A	p.Ser164Tyr	missense_variant	2/3	1	NM_021126.8	ENSP00000411719.3		P25325-2

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000650

AC:

AN:

230752

Hom.:

AF XY:

0.0000784

AC XY:

AN XY:

127530

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:

0.000132

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.000151

AC:

218

AN:

1446194

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

109

AN XY:

719990

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.000179

Gnomad4 OTH exome

AF:

0.000299

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000965

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:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000192

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000497

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

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

Sep 03, 2024

The c.491C>A (p.S164Y) alteration is located in exon 2 (coding exon 2) of the MPST gene. This alteration results from a C to A substitution at nucleotide position 491, causing the serine (S) at amino acid position 164 to be replaced by a tyrosine (Y). 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

0.23

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;T;T;.;.;T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

.;.;.;D;.;D;D

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.45

T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Pathogenic

3.8

H;H;H;.;.;H;.

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-4.0

D;D;D;.;D;D;.

REVEL

Benign

0.22

Sift

Uncertain

0.0010

D;D;D;.;D;D;.

Sift4G

Uncertain

0.011

D;D;D;D;D;D;D

Polyphen

0.99

D;D;D;.;D;D;D

Vest4

0.41

MVP

0.75

ClinPred

0.80

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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