Genetic Variant MPST:c.656-226G>A (chr22-37028990-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021126.8(MPST):c.656-226G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 544,600 control chromosomes in the GnomAD database, including 56,266 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 21030 hom., cov: 32)

Exomes 𝑓: 0.41 ( 35236 hom. )

Consequence

MPST
NM_021126.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.06

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

encephalopathy due to beta-mercaptolactate-cysteine disulfiduria
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

MPST links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021126.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MPST	NM_021126.8	MANE Select	c.656-226G>A	intron	N/A	NP_066949.2	P25325-2
MPST	NM_001013436.4		c.596-226G>A	intron	N/A	NP_001013454.1	P25325-1
MPST	NM_001130517.4		c.596-226G>A	intron	N/A	NP_001123989.1	P25325-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MPST	ENST00000429360.6	TSL:1 MANE Select	c.656-226G>A	intron	N/A	ENSP00000411719.3	P25325-2
MPST	ENST00000401419.7	TSL:1	c.596-226G>A	intron	N/A	ENSP00000384812.3	P25325-1
MPST	ENST00000865002.1		c.1004-226G>A	intron	N/A	ENSP00000535061.1

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74554

AN:

151876

Hom.:

20987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.777

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.385

Gnomad EAS

AF:

0.618

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.439

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.469

GnomAD4 exome

AF:

0.407

AC:

159877

AN:

392606

Hom.:

35236

Cov.:

AF XY:

0.404

AC XY:

82938

AN XY:

205054

show subpopulations

African (AFR)

AF:

0.781

AC:

8918

AN:

11412

American (AMR)

AF:

0.373

AC:

5489

AN:

14708

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

4658

AN:

12314

East Asian (EAS)

AF:

0.686

AC:

18630

AN:

27150

South Asian (SAS)

AF:

0.400

AC:

15480

AN:

38680

European-Finnish (FIN)

AF:

0.382

AC:

9361

AN:

24530

Middle Eastern (MID)

AF:

0.440

AC:

779

AN:

1770

European-Non Finnish (NFE)

AF:

0.364

AC:

87032

AN:

239100

Other (OTH)

AF:

0.415

AC:

9530

AN:

22942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

4195

8390

12586

16781

20976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

622

1244

1866

2488

3110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.491

AC:

74644

AN:

151994

Hom.:

21030

Cov.:

AF XY:

0.489

AC XY:

36330

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.778

AC:

32235

AN:

41448

American (AMR)

AF:

0.382

AC:

5835

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

1338

AN:

3472

East Asian (EAS)

AF:

0.618

AC:

3197

AN:

5172

South Asian (SAS)

AF:

0.406

AC:

1958

AN:

4820

European-Finnish (FIN)

AF:

0.382

AC:

4025

AN:

10542

Middle Eastern (MID)

AF:

0.452

AC:

132

AN:

292

European-Non Finnish (NFE)

AF:

0.362

AC:

24597

AN:

67962

Other (OTH)

AF:

0.465

AC:

982

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1714

3428

5143

6857

8571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.394

Hom.:

16611

Bravo

AF:

0.505

Asia WGS

AF:

0.469

AC:

1633

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0030

(source)

DANN

Benign

0.33

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over