11-134356378-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001370461.1(GLB1L2):c.636G>T(p.Met212Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
GLB1L2
NM_001370461.1 missense
NM_001370461.1 missense
Scores
4
13
2
Clinical Significance
Conservation
PhyloP100: 5.52
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.808
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLB1L2 | NM_001370461.1 | c.636G>T | p.Met212Ile | missense_variant | 6/19 | ENST00000535456.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLB1L2 | ENST00000535456.7 | c.636G>T | p.Met212Ile | missense_variant | 6/19 | 1 | NM_001370461.1 | P1 | |
GLB1L2 | ENST00000529077.5 | n.940G>T | non_coding_transcript_exon_variant | 3/22 | 1 | ||||
GLB1L2 | ENST00000531081.5 | n.176G>T | non_coding_transcript_exon_variant | 2/4 | 4 | ||||
GLB1L2 | ENST00000533324.2 | n.118G>T | non_coding_transcript_exon_variant | 2/7 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251416Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135872
GnomAD3 exomes
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460256Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 726574
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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?
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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 02, 2022 | The c.636G>T (p.M212I) alteration is located in exon 6 (coding exon 6) of the GLB1L2 gene. This alteration results from a G to T substitution at nucleotide position 636, causing the methionine (M) at amino acid position 212 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MutPred
Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);
MVP
MPC
0.32
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at