Variant 11-134359132-G-T 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.724G>T(p.Val242Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000625 in 1,600,406 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

GLB1L2
NM_001370461.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.152

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.724G>T	p.Val242Phe	missense_variant	7/19	ENST00000535456.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GLB1L2	ENST00000535456.7 linkuse as main transcript	c.724G>T	p.Val242Phe	missense_variant	7/19	1	NM_001370461.1	P1
GLB1L2	ENST00000529077.5 linkuse as main transcript	n.1028G>T		non_coding_transcript_exon_variant	4/22	1
GLB1L2	ENST00000531081.5 linkuse as main transcript	n.264G>T		non_coding_transcript_exon_variant	3/4	4
GLB1L2	ENST00000533324.2 linkuse as main transcript	n.206G>T		non_coding_transcript_exon_variant	3/7	3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000416

AC:

AN:

240374

Hom.:

AF XY:

0.00

AC XY:

AN XY:

129922

show subpopulations

Gnomad AFR exome

AF:

0.0000630

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1448180

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719742

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000145

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

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

Jun 27, 2022

The c.724G>T (p.V242F) alteration is located in exon 7 (coding exon 7) of the GLB1L2 gene. This alteration results from a G to T substitution at nucleotide position 724, causing the valine (V) at amino acid position 242 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

0.14

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Uncertain

0.010

Cadd

Benign

9.1

Dann

Uncertain

0.98

DEOGEN2

Uncertain

0.70

D;D

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.77

T;.

M_CAP

Uncertain

0.092

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Uncertain

0.33

MutationAssessor

Uncertain

2.9

M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.1

D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.021

D;D

Polyphen

0.73

P;P

Vest4

0.52

MutPred

0.54

Gain of ubiquitination at K239 (P = 0.0773);Gain of ubiquitination at K239 (P = 0.0773);

MVP

0.22

MPC

0.57

ClinPred

0.98

GERP RS

-9.3

Varity_R

0.16

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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