11-134359106-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370461.1(GLB1L2):c.698A>G(p.Asn233Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,452,046 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: GLB1L2 NM_001370461.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30194992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLB1L2	NM_001370461.1	c.698A>G	p.Asn233Ser	missense_variant	7/19	ENST00000535456.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLB1L2	ENST00000535456.7	c.698A>G	p.Asn233Ser	missense_variant	7/19	1	NM_001370461.1	P1
GLB1L2	ENST00000529077.5	n.1002A>G		non_coding_transcript_exon_variant	4/22	1
GLB1L2	ENST00000531081.5	n.238A>G		non_coding_transcript_exon_variant	3/4	4
GLB1L2	ENST00000533324.2	n.180A>G		non_coding_transcript_exon_variant	3/7	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1452046 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 721994

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: 0.00000271

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 34

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 26, 2021

The c.698A>G (p.N233S) alteration is located in exon 7 (coding exon 7) of the GLB1L2 gene. This alteration results from a A to G substitution at nucleotide position 698, causing the asparagine (N) at amino acid position 233 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T;.
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.43
Sift	Benign	0.21	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.10	B;B
Vest4		0.45
MutPred		0.50		Gain of catalytic residue at K234 (P = 0.039);Gain of catalytic residue at K234 (P = 0.039);
MVP		0.37
MPC		0.15
ClinPred		0.93	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr11-134229000;