22-37029323-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_021126.8(MPST):c.763G>A(p.Glu255Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
MPST
NM_021126.8 missense
NM_021126.8 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 4.42
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11539313).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MPST | NM_021126.8 | c.763G>A | p.Glu255Lys | missense_variant | 3/3 | ENST00000429360.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MPST | ENST00000429360.6 | c.763G>A | p.Glu255Lys | missense_variant | 3/3 | 1 | NM_021126.8 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251350Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135906
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GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461852Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727234
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74378
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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 | May 10, 2022 | The c.763G>A (p.E255K) alteration is located in exon 3 (coding exon 3) of the MPST gene. This alteration results from a G to A substitution at nucleotide position 763, causing the glutamic acid (E) at amino acid position 255 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.;L
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;.;N
REVEL
Benign
Sift
Benign
T;T;T;.;T
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;B;.;B
Vest4
MVP
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at