11-134344428-T-G

Variant names:

• chr11-134344428-T-G
• rs1416819108
• NM_001370461.1:c.326T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001370461.1(GLB1L2):​c.326T>G​(p.Phe109Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. F109S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: GLB1L2 NM_001370461.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.918

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370461.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLB1L2	NM_001370461.1	MANE Select	c.326T>G	p.Phe109Cys	missense	Exon 3 of 19	NP_001357390.1	Q8IW92
	GLB1L2	NM_001370460.1		c.326T>G	p.Phe109Cys	missense	Exon 3 of 20	NP_001357389.1
	GLB1L2	NM_138342.4		c.326T>G	p.Phe109Cys	missense	Exon 3 of 20	NP_612351.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLB1L2	ENST00000535456.7	TSL:1 MANE Select	c.326T>G	p.Phe109Cys	missense	Exon 3 of 19	ENSP00000444628.1	Q8IW92
	GLB1L2	ENST00000855671.1		c.326T>G	p.Phe109Cys	missense	Exon 3 of 18	ENSP00000525730.1
	GLB1L2	ENST00000855672.1		c.87-2897T>G		intron	N/A	ENSP00000525731.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.83	D
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		1.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Pathogenic	0.89
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.72		Loss of catalytic residue at F109 (P = 0.0537)
MVP		0.59
MPC		0.81
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.83
gMVP		0.96
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs1416819108; hg19: chr11-134214322;