Variant 11-134364332-G-C 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.738G>C(p.Leu246Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

GLB1L2
NM_001370461.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.61

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:

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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
GLB1L2	NM_001370461.1 linkuse as main transcript	c.738G>C	p.Leu246Phe	missense_variant	8/19	ENST00000535456.7
GLB1L2	NM_001370460.1 linkuse as main transcript	c.900G>C	p.Leu300Phe	missense_variant	9/20
GLB1L2	NM_138342.4 linkuse as main transcript	c.738G>C	p.Leu246Phe	missense_variant	8/20
GLB1L2	XR_007062523.1 linkuse as main transcript	n.812G>C		non_coding_transcript_exon_variant	8/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GLB1L2	ENST00000535456.7 linkuse as main transcript	c.738G>C	p.Leu246Phe	missense_variant	8/19	1	NM_001370461.1	P1
GLB1L2	ENST00000529077.5 linkuse as main transcript	n.2813G>C		non_coding_transcript_exon_variant	7/22	1
GLB1L2	ENST00000531081.5 linkuse as main transcript	n.278G>C		non_coding_transcript_exon_variant	4/4	4
GLB1L2	ENST00000533324.2 linkuse as main transcript	n.220G>C		non_coding_transcript_exon_variant	4/7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251184

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461050

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726878

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:

0.00000810

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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

Dec 03, 2021

The c.738G>C (p.L246F) alteration is located in exon 8 (coding exon 8) of the GLB1L2 gene. This alteration results from a G to C substitution at nucleotide position 738, causing the leucine (L) at amino acid position 246 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

0.0

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.67

D;D

Eigen

Benign

-0.080

Eigen_PC

Benign

-0.046

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

T;.

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.59

D;D

MetaSVM

Pathogenic

0.82

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.6

D;D

REVEL

Uncertain

0.58

Sift

Benign

0.030

D;D

Sift4G

Benign

0.093

T;T

Polyphen

0.25

B;B

Vest4

0.54

MutPred

0.66

Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);

MVP

0.67

MPC

0.23

ClinPred

0.41

GERP RS

3.6

Varity_R

0.24

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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