chr1-43453697-C-G

Position:

chr1-43453697-C-G

Variant summary

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

The NM_001190880.3(HYI):c.97G>C(p.Glu33Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,437,294 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 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

HYI
NM_001190880.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0200

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:

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=0.0739792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYI	NM_001190880.3 linkuse as main transcript	c.97G>C	p.Glu33Gln	missense_variant	1/8	ENST00000372430.9
SZT2	NM_001365999.1 linkuse as main transcript	c.*3217C>G		3_prime_UTR_variant	72/72	ENST00000634258.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYI	ENST00000372430.9 linkuse as main transcript	c.97G>C	p.Glu33Gln	missense_variant	1/8	1	NM_001190880.3	P1	Q5T013-1
SZT2	ENST00000634258.3 linkuse as main transcript	c.*3217C>G		3_prime_UTR_variant	72/72	5	NM_001365999.1	P1	Q5T011-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000216

AC:

AN:

46224

Hom.:

AF XY:

0.0000358

AC XY:

AN XY:

27922

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:

0.0000979

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000282

AC:

363

AN:

1285230

Hom.:

Cov.:

AF XY:

0.000275

AC XY:

174

AN XY:

632704

show subpopulations

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:

0.000302

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000324

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000125

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.000106

ExAC

AF:

0.0000385

AC:

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

Jul 06, 2021

The c.97G>C (p.E33Q) alteration is located in exon 1 (coding exon 1) of the HYI gene. This alteration results from a G to C substitution at nucleotide position 97, causing the glutamic acid (E) at amino acid position 33 to be replaced by a glutamine (Q). 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

0.10

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.024

T;T;T;.;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.77

T;T;T;T;T

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.074

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.080

N;.;.;N;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.14

N;.;.;N;N

REVEL

Benign

0.026

Sift

Benign

0.37

T;.;.;T;T

Sift4G

Benign

0.60

T;T;T;T;T

Polyphen

0.0

B;.;.;.;.

Vest4

0.071

MutPred

0.51

Gain of MoRF binding (P = 0.0718);Gain of MoRF binding (P = 0.0718);Gain of MoRF binding (P = 0.0718);Gain of MoRF binding (P = 0.0718);Gain of MoRF binding (P = 0.0718);

MVP

0.39

MPC

0.055

ClinPred

0.054

GERP RS

-0.070

Varity_R

0.17

gMVP

0.66

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over