22-37028990-G-C

Variant names:

• chr22-37028990-G-C
• rs5750373
• NM_021126.8:c.656-226G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021126.8(MPST):​c.656-226G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MPST NM_021126.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 6 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 393480 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 205528

African (AFR) AF: 0.00 AC: 0 AN: 11432

American (AMR) AF: 0.00 AC: 0 AN: 14748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12340

East Asian (EAS) AF: 0.00 AC: 0 AN: 27230

South Asian (SAS) AF: 0.00 AC: 0 AN: 38788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1772

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 239602

Other (OTH) AF: 0.00 AC: 0 AN: 22990

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 16611

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
DANN	Benign	0.42
PhyloP100		-2.1

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

Other links and lift over

dbSNP: rs5750373; hg19: chr22-37425031;