11-134277351-G-T

Position:

• chr11-134277351-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080407.3(GLB1L3):​c.49G>T​(p.Ala17Ser) 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 benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GLB1L3 NM_001080407.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.39

Genes affected

GLB1L3 (HGNC:25147): (galactosidase beta 1 like 3) Predicted to enable beta-galactosidase activity. Predicted to be involved in carbohydrate metabolic process. Predicted to be active in vacuole. [provided by Alliance of Genome Resources, Apr 2022]

GLB1L3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06812197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLB1L3	NM_001080407.3	c.49G>T	p.Ala17Ser	missense_variant	2/20	ENST00000431683.7	NP_001073876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLB1L3	ENST00000431683.7	c.49G>T	p.Ala17Ser	missense_variant	2/20	5	NM_001080407.3	ENSP00000396615.2
GLB1L3	ENST00000389887.9	c.49G>T	p.Ala17Ser	missense_variant	2/10	1		ENSP00000374537.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Sep 27, 2024

The c.49G>T (p.A17S) alteration is located in exon 2 (coding exon 2) of the GLB1L3 gene. This alteration results from a G to T substitution at nucleotide position 49, causing the alanine (A) at amino acid position 17 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	0.11
BayesDel_addAF	Benign	-0.0060	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	0.031
DANN	Benign	0.90
DEOGEN2	Benign	0.023	.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.068	T;T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.28
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.037	D;T
Polyphen		0.0080	B;B
Vest4		0.14
MutPred		0.38		Gain of disorder (P = 0.0126);Gain of disorder (P = 0.0126);
MVP		0.25
MPC		0.035
ClinPred		0.064	T
GERP RS		-9.3
Varity_R		0.067
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1940431452; hg19: chr11-134147245;