dbSNP rs776997759: HYI:p.Arg118Pro (chr1-43452278-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001190880.3(HYI):c.353G>C(p.Arg118Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R118Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

HYI
NM_001190880.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.69

Variant links:

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]

HYI links:

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]

SZT2 links:

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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=0.23382929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYI	NM_001190880.3 link	c.353G>C	p.Arg118Pro	missense_variant	Exon 3 of 8	ENST00000372430.9	NP_001177809.1	Q5T013-1
SZT2	NM_001365999.1 link	c.*1798C>G		3_prime_UTR_variant	Exon 72 of 72	ENST00000634258.3	NP_001352928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYI	ENST00000372430.9 link	c.353G>C	p.Arg118Pro	missense_variant	Exon 3 of 8	1	NM_001190880.3	ENSP00000361507.4		Q5T013-1J9JIE9
SZT2	ENST00000634258.3 link	c.*1798C>G		3_prime_UTR_variant	Exon 72 of 72	5	NM_001365999.1	ENSP00000489255.1		Q5T011-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250836

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135566

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.27

T;T;T;.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.73

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.76

T;T;T;T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

L;.;.;L;.

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.2

D;.;.;D;D

REVEL

Benign

0.27

Sift

Benign

0.13

T;.;.;T;T

Sift4G

Benign

0.11

T;D;T;D;T

Polyphen

0.028

B;.;.;.;.

Vest4

0.43

MutPred

0.55

Loss of MoRF binding (P = 9e-04);.;.;Loss of MoRF binding (P = 9e-04);Loss of MoRF binding (P = 9e-04);

MVP

0.37

MPC

0.088

ClinPred

0.12

GERP RS

1.4

Varity_R

0.46

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over