1-43453702-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001190880.3(HYI):c.92G>A(p.Gly31Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000788 in 1,269,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.9e-7 ( 0 hom. )
Consequence
HYI
NM_001190880.3 missense
NM_001190880.3 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 4.88
Genes affected
HYI (HGNC:26948): (hydroxypyruvate isomerase (putative)) This gene encodes a putative hydroxypyruvate isomerase, which likely catalyzes the conversion of hydroxypyruvate to 2-hydroxy-3-oxopropanoate, and may be involved in carbohydrate transport and metabolism. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
SZT2 (HGNC:29040): (SZT2 subunit of KICSTOR complex) The protein encoded by this gene is expressed in the brain, predominantly in the parietal and frontal cortex as well as in dorsal root ganglia. It is localized to the peroxisome, and is implicated in resistance to oxidative stress. It likely functions by increasing superoxide dismutase (SOD) activity, but itself has no direct SOD activity. Studies in mice show that this gene confers low seizure threshold, and may also enhance epileptogenesis. [provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.986
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HYI | NM_001190880.3 | c.92G>A | p.Gly31Asp | missense_variant | 1/8 | ENST00000372430.9 | |
SZT2 | NM_001365999.1 | c.*3222C>T | 3_prime_UTR_variant | 72/72 | ENST00000634258.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HYI | ENST00000372430.9 | c.92G>A | p.Gly31Asp | missense_variant | 1/8 | 1 | NM_001190880.3 | P1 | |
SZT2 | ENST00000634258.3 | c.*3222C>T | 3_prime_UTR_variant | 72/72 | 5 | NM_001365999.1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 7.88e-7 AC: 1AN: 1269372Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0AN XY: 623594
GnomAD4 exome
AF:
AC:
1
AN:
1269372
Hom.:
Cov.:
40
AF XY:
AC XY:
0
AN XY:
623594
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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 11, 2022 | The c.92G>A (p.G31D) alteration is located in exon 1 (coding exon 1) of the HYI gene. This alteration results from a G to A substitution at nucleotide position 92, causing the glycine (G) at amino acid position 31 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
T;D;D;.;D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.;.;H;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;.;D;D
REVEL
Pathogenic
Sift
Uncertain
D;.;.;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
D;.;.;.;.
Vest4
MutPred
Loss of glycosylation at S30 (P = 0.029);Loss of glycosylation at S30 (P = 0.029);Loss of glycosylation at S30 (P = 0.029);Loss of glycosylation at S30 (P = 0.029);Loss of glycosylation at S30 (P = 0.029);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.