chr3-33024297-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000404.4(GLB1):​c.1097C>T​(p.Pro366Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P366H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GLB1
NM_000404.4 missense

Scores

11
4
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.85
Variant links:
Genes affected
GLB1 (HGNC:4298): (galactosidase beta 1) This gene encodes a member of the glycosyl hydrolase 35 family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature lysosomal enzyme. This enzyme catalyzes the hydrolysis of a terminal beta-linked galactose residue from ganglioside substrates and other glycoconjugates. Mutations in this gene may result in GM1-gangliosidosis and Morquio B syndrome. [provided by RefSeq, Nov 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.869

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLB1NM_000404.4 linkuse as main transcriptc.1097C>T p.Pro366Leu missense_variant 11/16 ENST00000307363.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLB1ENST00000307363.10 linkuse as main transcriptc.1097C>T p.Pro366Leu missense_variant 11/161 NM_000404.4 P2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461046
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726792
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Pathogenic
0.53
D
BayesDel_noAF
Pathogenic
0.53
CADD
Uncertain
25
DANN
Uncertain
1.0
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.94
.;.;D
M_CAP
Pathogenic
0.50
D
MetaRNN
Pathogenic
0.87
D;D;D
MetaSVM
Pathogenic
1.1
D
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-8.9
D;D;D
REVEL
Pathogenic
0.89
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.0040
D;D;D
Polyphen
1.0
.;.;D
Vest4
0.78
MutPred
0.60
Loss of disorder (P = 0.0171);.;.;
MVP
0.98
MPC
0.88
ClinPred
1.0
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.92

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: rs797045010; hg19: chr3-33065789; API