Variant chr22-37024382-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP4_StrongBP6_ModerateBS2

The NM_021126.8(MPST):c.227G>T(p.Gly76Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,544,770 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 29 hom. )

Consequence

MPST
NM_021126.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.73

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP3

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

BP4

Computational evidence support a benign effect (MetaRNN=0.025369227).

BP6

Variant 22-37024382-G-T is Benign according to our data. Variant chr22-37024382-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3037468.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPST	NM_021126.8 linkuse as main transcript	c.227G>T	p.Gly76Val	missense_variant	2/3	ENST00000429360.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPST	ENST00000429360.6 linkuse as main transcript	c.227G>T	p.Gly76Val	missense_variant	2/3	1	NM_021126.8		P25325-2

Frequencies

GnomAD3 genomes

AF:

0.00261

AC:

398

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00470

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00194

AC:

278

AN:

143196

Hom.:

AF XY:

0.00200

AC XY:

156

AN XY:

78050

show subpopulations

Gnomad AFR exome

AF:

0.000656

Gnomad AMR exome

AF:

0.000998

Gnomad ASJ exome

AF:

0.000128

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000911

Gnomad FIN exome

AF:

0.000848

Gnomad NFE exome

AF:

0.00424

Gnomad OTH exome

AF:

0.00170

GnomAD4 exome

AF:

0.00436

AC:

6074

AN:

1392430

Hom.:

Cov.:

AF XY:

0.00423

AC XY:

2904

AN XY:

687126

show subpopulations

Gnomad4 AFR exome

AF:

0.000640

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.000282

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000381

Gnomad4 FIN exome

AF:

0.000725

Gnomad4 NFE exome

AF:

0.00537

Gnomad4 OTH exome

AF:

0.00328

GnomAD4 genome

AF:

0.00261

AC:

398

AN:

152340

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00471

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00399

Hom.:

Bravo

AF:

0.00274

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000707

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.000933

AC:

106

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MPST-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 12, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

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

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.96

FATHMM_MKL

Pathogenic

0.97

MetaRNN

Benign

0.025

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

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

4.9

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-8.7

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

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

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

Sift4G

Pathogenic

0.0010

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

Polyphen

1.0

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

Vest4

0.86

MVP

0.91

ClinPred

0.58

GERP RS

5.5

Varity_R

0.99

gMVP

0.82

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