11-134332111-T-A

Position:

• chr11-134332111-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370461.1(GLB1L2):​c.50T>A​(p.Leu17Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,439,110 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: GLB1L2 NM_001370461.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.964

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 (HGNC:):

ACMG classification

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	Protein	UniProt
GLB1L2	NM_001370461.1	c.50T>A	p.Leu17Gln	missense_variant	1/19	ENST00000535456.7	NP_001357390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLB1L2	ENST00000535456.7	c.50T>A	p.Leu17Gln	missense_variant	1/19	1	NM_001370461.1	ENSP00000444628.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000104 AC: 15 AN: 1439110 Hom.: 0 Cov.: 30 AF XY: 0.00000980 AC XY: 7 AN XY: 714490

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: 0.0000136

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2023

The c.50T>A (p.L17Q) alteration is located in exon 1 (coding exon 1) of the GLB1L2 gene. This alteration results from a T to A substitution at nucleotide position 50, causing the leucine (L) at amino acid position 17 to be replaced by a glutamine (Q). 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	0.27
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T;T
Eigen	Benign	-0.025
Eigen_PC	Benign	-0.033
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.53	T;.
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.93	N;N
REVEL	Uncertain	0.55
Sift	Benign	0.030	D;D
Sift4G	Uncertain	0.033	D;D
Polyphen		0.95	P;P
Vest4		0.61
MutPred		0.52		Loss of stability (P = 0.0193);Loss of stability (P = 0.0193);
MVP		0.47
MPC		0.53
ClinPred		0.94	D
GERP RS		2.9
Varity_R		0.14
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-134202005;