Variant 6-38682852-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006708.3(GLO1):c.332A>C(p.Glu111Ala) variant causes a missense change. The variant allele was found at a frequency of 0.414 in 1,595,116 control chromosomes in the GnomAD database, including 143,660 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.38 ( 11571 hom., cov: 31)

Exomes 𝑓: 0.42 ( 132089 hom. )

Consequence

GLO1
NM_006708.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.24

Variant links:

Genes affected

GLO1 (HGNC:4323): (glyoxalase I) The enzyme encoded by this gene is responsible for the catalysis and formation of S-lactoyl-glutathione from methylglyoxal condensation and reduced glutatione. Glyoxalase I is linked to HLA and is localized to 6p21.3-p21.1, between HLA and the centromere. [provided by RefSeq, Jul 2008]

GLO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020796955).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLO1	NM_006708.3 linkuse as main transcript	c.332A>C	p.Glu111Ala	missense_variant	4/6	ENST00000373365.5	NP_006699.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLO1	ENST00000373365.5 linkuse as main transcript	c.332A>C	p.Glu111Ala	missense_variant	4/6	1	NM_006708.3	ENSP00000362463	P1	Q04760-1
GLO1	ENST00000470973.1 linkuse as main transcript	n.364A>C		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57876

AN:

151874

Hom.:

11567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.359

GnomAD3 exomes

AF:

0.361

AC:

90647

AN:

251032

Hom.:

17523

AF XY:

0.360

AC XY:

48810

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.332

Gnomad AMR exome

AF:

0.351

Gnomad ASJ exome

AF:

0.329

Gnomad EAS exome

AF:

0.130

Gnomad SAS exome

AF:

0.257

Gnomad FIN exome

AF:

0.356

Gnomad NFE exome

AF:

0.437

Gnomad OTH exome

AF:

0.374

GnomAD4 exome

AF:

0.418

AC:

602968

AN:

1443124

Hom.:

132089

Cov.:

AF XY:

0.413

AC XY:

297028

AN XY:

719032

show subpopulations

Gnomad4 AFR exome

AF:

0.321

Gnomad4 AMR exome

AF:

0.357

Gnomad4 ASJ exome

AF:

0.325

Gnomad4 EAS exome

AF:

0.0903

Gnomad4 SAS exome

AF:

0.254

Gnomad4 FIN exome

AF:

0.362

Gnomad4 NFE exome

AF:

0.455

Gnomad4 OTH exome

AF:

0.395

GnomAD4 genome

AF:

0.381

AC:

57910

AN:

151992

Hom.:

11571

Cov.:

AF XY:

0.374

AC XY:

27766

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.329

Gnomad4 AMR

AF:

0.400

Gnomad4 ASJ

AF:

0.326

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.346

Gnomad4 NFE

AF:

0.445

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.416

Hom.:

15649

Bravo

AF:

0.381

TwinsUK

AF:

0.452

AC:

1677

ALSPAC

AF:

0.466

AC:

1795

ESP6500AA

AF:

0.349

AC:

1539

ESP6500EA

AF:

0.442

AC:

3800

ExAC

AF:

0.362

AC:

43910

Asia WGS

AF:

0.204

AC:

708

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autism, susceptibility to, 1

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Dec 30, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.20

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.13

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.67

MutationTaster

Benign

0.000088

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.0

REVEL

Benign

0.053

Sift

Benign

0.59

Sift4G

Benign

0.46

Polyphen

0.0

Vest4

0.063

MPC

0.14

ClinPred

0.027

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.44

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