22-37024255-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021126.8(MPST):​c.100C>A​(p.Gln34Lys) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q34H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MPST
NM_021126.8 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43
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]

Genome browser will be placed here

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=0.1370891).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MPSTNM_021126.8 linkuse as main transcriptc.100C>A p.Gln34Lys missense_variant 2/3 ENST00000429360.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MPSTENST00000429360.6 linkuse as main transcriptc.100C>A p.Gln34Lys missense_variant 2/31 NM_021126.8 P25325-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1291538
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
632088
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756

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 submitterclinical testingAmbry GeneticsJan 31, 2022The c.100C>A (p.Q34K) alteration is located in exon 2 (coding exon 2) of the MPST gene. This alteration results from a C to A substitution at nucleotide position 100, causing the glutamine (Q) at amino acid position 34 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
15
DANN
Benign
0.96
DEOGEN2
Benign
0.0033
T;T;T;.;.;T;.
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.40
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.81
.;.;.;T;.;T;T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.14
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.32
N;N;N;.;.;N;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
0.23
N;N;N;.;N;N;.
REVEL
Benign
0.11
Sift
Benign
1.0
T;T;T;.;T;T;.
Sift4G
Benign
1.0
T;T;T;T;T;T;T
Polyphen
0.0
B;B;B;.;B;B;B
Vest4
0.13
MutPred
0.47
Gain of methylation at Q14 (P = 0.0241);Gain of methylation at Q14 (P = 0.0241);Gain of methylation at Q14 (P = 0.0241);.;Gain of methylation at Q14 (P = 0.0241);Gain of methylation at Q14 (P = 0.0241);Gain of methylation at Q14 (P = 0.0241);
MVP
0.43
ClinPred
0.099
T
GERP RS
4.5
Varity_R
0.17
gMVP
0.58

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.

Other links and lift over

dbSNP: rs1021850175; hg19: chr22-37420296; API