rs5750373

Positions:

• chr22-37028990-G-A
• chr22-37028990-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPST	NM_021126.8	c.656-226G>A		intron_variant		ENST00000429360.6	NP_066949.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPST	ENST00000429360.6	c.656-226G>A		intron_variant		1	NM_021126.8	ENSP00000411719.3

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74554 AN: 151876 Hom.: 20987 Cov.: 32

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.: 4 AF XY: 0.404 AC XY: 82938 AN XY: 205054

Gnomad4 AFR exome AF: 0.781

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.686

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.415

GnomAD4 genome AF: 0.491 AC: 74644 AN: 151994 Hom.: 21030 Cov.: 32 AF XY: 0.489 AC XY: 36330 AN XY: 74266

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.465

Alfa AF: 0.374 Hom.: 11066

Bravo AF: 0.505

Asia WGS AF: 0.469 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0030
DANN	Benign	0.33

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

Other links and lift over

dbSNP: rs5750373; hg19: chr22-37425031;