Variant chr11-134356324-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370461.1(GLB1L2):c.582T>G(p.Ile194Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

GLB1L2
NM_001370461.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.539

Variant links:

Genes affected

GLB1L2 (HGNC:25129): (galactosidase beta 1 like 2) Predicted to enable beta-galactosidase activity. Predicted to be involved in carbohydrate metabolic process. Predicted to be located in extracellular region. Predicted to be active in vacuole. [provided by Alliance of Genome Resources, Apr 2022]

GLB1L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLB1L2	NM_001370461.1 linkuse as main transcript	c.582T>G	p.Ile194Met	missense_variant	6/19	ENST00000535456.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GLB1L2	ENST00000535456.7 linkuse as main transcript	c.582T>G	p.Ile194Met	missense_variant	6/19	1	NM_001370461.1	P1
GLB1L2	ENST00000529077.5 linkuse as main transcript	n.886T>G		non_coding_transcript_exon_variant	3/22	1
GLB1L2	ENST00000531081.5 linkuse as main transcript	n.122T>G		non_coding_transcript_exon_variant	2/4	4
GLB1L2	ENST00000533324.2 linkuse as main transcript	n.64T>G		non_coding_transcript_exon_variant	2/7	3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251480

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461796

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727194

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

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

Aug 30, 2021

The c.582T>G (p.I194M) alteration is located in exon 6 (coding exon 6) of the GLB1L2 gene. This alteration results from a T to G substitution at nucleotide position 582, causing the isoleucine (I) at amino acid position 194 to be replaced by a methionine (M). 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

0.21

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.84

D;D

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.79

T;.

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.65

D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.9

H;H

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.9

D;D

REVEL

Pathogenic

0.81

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.53

MVP

0.44

MPC

0.66

ClinPred

0.98

GERP RS

-4.4

Varity_R

0.53

gMVP

0.94

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