Variant 1-43453627-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_001190880.3(HYI):c.167G>A(p.Gly56Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00181 in 1,496,150 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 3 hom. )

Consequence

HYI
NM_001190880.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.78

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22030288).

BP6

Variant 1-43453627-C-T is Benign according to our data. Variant chr1-43453627-C-T is described in ClinVar as [Benign]. Clinvar id is 1686343.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYI	NM_001190880.3 linkuse as main transcript	c.167G>A	p.Gly56Glu	missense_variant	1/8	ENST00000372430.9
SZT2	NM_001365999.1 linkuse as main transcript	c.*3147C>T		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.167G>A	p.Gly56Glu	missense_variant	1/8	1	NM_001190880.3	P1	Q5T013-1
SZT2	ENST00000634258.3 linkuse as main transcript	c.*3147C>T		3_prime_UTR_variant	72/72	5	NM_001365999.1	P1	Q5T011-1

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

198

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00224

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00105

AC:

AN:

87656

Hom.:

AF XY:

0.000965

AC XY:

AN XY:

49764

show subpopulations

Gnomad AFR exome

AF:

0.000864

Gnomad AMR exome

AF:

0.00149

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000118

Gnomad FIN exome

AF:

0.000335

Gnomad NFE exome

AF:

0.00188

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00187

AC:

2509

AN:

1343908

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1182

AN XY:

662516

show subpopulations

Gnomad4 AFR exome

AF:

0.000298

Gnomad4 AMR exome

AF:

0.00129

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000176

Gnomad4 FIN exome

AF:

0.000295

Gnomad4 NFE exome

AF:

0.00220

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00129

AC:

197

AN:

152242

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00222

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00153

Hom.:

Bravo

AF:

0.00127

ExAC

AF:

0.000322

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.21

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.36

T;T;T;.;T

Eigen

Benign

-0.014

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.86

D;D;D;D;D

M_CAP

Pathogenic

0.89

MetaRNN

Benign

0.22

T;T;T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.8

M;.;.;M;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-4.3

D;.;.;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0020

D;.;.;D;D

Sift4G

Uncertain

0.022

D;D;D;T;D

Polyphen

0.42

B;.;.;.;.

Vest4

0.57

MVP

0.62

MPC

0.34

ClinPred

0.066

GERP RS

3.7

Varity_R

0.65

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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