rs141158872

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001190880.3(HYI):c.302G>A(p.Gly101Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000487 in 1,553,608 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 3 hom. )

Consequence

HYI
NM_001190880.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.70

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011427939).

BP6

Variant 1-43453395-C-T is Benign according to our data. Variant chr1-43453395-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYI	NM_001190880.3 link	c.302G>A	p.Gly101Asp	missense_variant	Exon 2 of 8	ENST00000372430.9	NP_001177809.1	Q5T013-1
SZT2	NM_001365999.1 link	c.*2915C>T		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.302G>A	p.Gly101Asp	missense_variant	Exon 2 of 8	1	NM_001190880.3	ENSP00000361507.4		Q5T013-1J9JIE9
SZT2	ENST00000634258.3 link	c.*2915C>T		3_prime_UTR_variant	Exon 72 of 72	5	NM_001365999.1	ENSP00000489255.1		Q5T011-1

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

381

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00857

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000708

AC:

112

AN:

158168

Hom.:

AF XY:

0.000536

AC XY:

AN XY:

84032

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.000387

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:

0.0000502

Gnomad OTH exome

AF:

0.000459

GnomAD4 exome

AF:

0.000268

AC:

375

AN:

1401390

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

152

AN XY:

691666

show subpopulations

Gnomad4 AFR exome

AF:

0.00980

Gnomad4 AMR exome

AF:

0.000489

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:

0.00000370

Gnomad4 OTH exome

AF:

0.000638

GnomAD4 genome

AF:

0.00250

AC:

381

AN:

152218

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

178

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00854

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000538

Hom.:

Bravo

AF:

0.00310

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00765

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000549

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 24, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.11

T;.;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.84

T;T;D

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.78

N;N;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.0020

B;.;.

Vest4

0.33

MVP

0.57

MPC

0.073

ClinPred

0.011

GERP RS

2.4

Varity_R

0.096

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