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GeneBe

11-134332083-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370461.1(GLB1L2):c.22C>T(p.Arg8Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000053 in 1,585,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

GLB1L2
NM_001370461.1 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23965475).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLB1L2NM_001370461.1 linkuse as main transcriptc.22C>T p.Arg8Trp missense_variant 1/19 ENST00000535456.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLB1L2ENST00000535456.7 linkuse as main transcriptc.22C>T p.Arg8Trp missense_variant 1/191 NM_001370461.1 P1

Frequencies

GnomAD3 genomes
AF:
0.000330
AC:
50
AN:
151680
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00118
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000387
AC:
8
AN:
206792
Hom.:
0
AF XY:
0.0000356
AC XY:
4
AN XY:
112368
show subpopulations
Gnomad AFR exome
AF:
0.000526
Gnomad AMR exome
AF:
0.0000661
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:
0.0000237
AC:
34
AN:
1434014
Hom.:
0
Cov.:
30
AF XY:
0.0000211
AC XY:
15
AN XY:
711434
show subpopulations
Gnomad4 AFR exome
AF:
0.000783
Gnomad4 AMR exome
AF:
0.0000726
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000845
GnomAD4 genome
AF:
0.000329
AC:
50
AN:
151792
Hom.:
0
Cov.:
31
AF XY:
0.000323
AC XY:
24
AN XY:
74196
show subpopulations
Gnomad4 AFR
AF:
0.00118
Gnomad4 AMR
AF:
0.0000654
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
Alfa
AF:
0.000334
Hom.:
0
Bravo
AF:
0.000344
ESP6500AA
AF:
0.000912
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000585
AC:
7

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 submitterclinical testingAmbry GeneticsJun 06, 2022The c.22C>T (p.R8W) alteration is located in exon 1 (coding exon 1) of the GLB1L2 gene. This alteration results from a C to T substitution at nucleotide position 22, causing the arginine (R) at amino acid position 8 to be replaced by a tryptophan (W). 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
0.23
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Uncertain
0.030
Cadd
Pathogenic
28
Dann
Uncertain
1.0
DEOGEN2
Benign
0.018
T;T
Eigen
Benign
0.066
Eigen_PC
Benign
0.060
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.70
T;.
M_CAP
Uncertain
0.25
D
MetaRNN
Benign
0.24
T;T
MetaSVM
Uncertain
0.31
D
MutationAssessor
Benign
1.8
L;L
MutationTaster
Benign
0.96
N;N;N
PrimateAI
Pathogenic
0.79
T
PROVEAN
Benign
0.50
N;N
REVEL
Uncertain
0.40
Sift
Benign
0.031
D;D
Sift4G
Uncertain
0.033
D;D
Polyphen
1.0
D;D
Vest4
0.56
MVP
0.54
MPC
0.48
ClinPred
0.14
T
GERP RS
3.9
Varity_R
0.074
gMVP
0.76

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.

Other links and lift over

dbSNP: rs373596114; hg19: chr11-134201977; API