6-38682852-T-G

Variant names:

• chr6-38682852-T-G
• rs4746
• NM_006708.3:c.332A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/21 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
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.24
• Publications: 105 publications found

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]

ENSG00000298390 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006708.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLO1	NM_006708.3	MANE Select	c.332A>C	p.Glu111Ala	missense	Exon 4 of 6	NP_006699.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLO1	ENST00000373365.5	TSL:1 MANE Select	c.332A>C	p.Glu111Ala	missense	Exon 4 of 6	ENSP00000362463.3
	GLO1	ENST00000470973.1	TSL:2	n.364A>C		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000298390	ENST00000755274.1		n.480+28185T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57876 AN: 151874 Hom.: 11567 Cov.: 31

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

GnomAD2 exomes AF: 0.361 AC: 90647 AN: 251032 AF XY: 0.360

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 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.: 28 AF XY: 0.413 AC XY: 297028 AN XY: 719032

African (AFR) AF: 0.321 AC: 10631 AN: 33152

American (AMR) AF: 0.357 AC: 15946 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 8442 AN: 25988

East Asian (EAS) AF: 0.0903 AC: 3577 AN: 39610

South Asian (SAS) AF: 0.254 AC: 21792 AN: 85786

European-Finnish (FIN) AF: 0.362 AC: 19339 AN: 53366

Middle Eastern (MID) AF: 0.320 AC: 1838 AN: 5742

European-Non Finnish (NFE) AF: 0.455 AC: 497804 AN: 1095110

Other (OTH) AF: 0.395 AC: 23599 AN: 59744

GnomAD4 genome AF: 0.381 AC: 57910 AN: 151992 Hom.: 11571 Cov.: 31 AF XY: 0.374 AC XY: 27766 AN XY: 74310

African (AFR) AF: 0.329 AC: 13643 AN: 41450

American (AMR) AF: 0.400 AC: 6110 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1132 AN: 3468

East Asian (EAS) AF: 0.117 AC: 607 AN: 5182

South Asian (SAS) AF: 0.243 AC: 1173 AN: 4820

European-Finnish (FIN) AF: 0.346 AC: 3646 AN: 10524

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30271 AN: 67966

Other (OTH) AF: 0.355 AC: 747 AN: 2106

Alfa AF: 0.414 Hom.: 40974

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

Submissions by phenotype

Autism, susceptibility to, 1 Uncertain:1

Dec 30, 2010

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.13
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	N
PhyloP100		4.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.053
Sift	Benign	0.59	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.063
MPC		0.14
ClinPred		0.027	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.44
Mutation Taster		=92/8	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		1.0
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

Other links and lift over

dbSNP: rs4746; hg19: chr6-38650628; COSMIC: COSV64905249;