11-134282092-A-G

Position:

• chr11-134282092-A-G

Variant summary

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

The NM_001080407.3(GLB1L3):​c.499A>G​(p.Ser167Gly) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLB1L3 NM_001080407.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0820

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34511447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLB1L3	NM_001080407.3	c.499A>G	p.Ser167Gly	missense_variant	5/20	ENST00000431683.7	NP_001073876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLB1L3	ENST00000431683.7	c.499A>G	p.Ser167Gly	missense_variant	5/20	5	NM_001080407.3	ENSP00000396615.2
GLB1L3	ENST00000389887.9	c.499A>G	p.Ser167Gly	missense_variant	5/10	1		ENSP00000374537.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.08e-7 AC: 1 AN: 1412228 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 697558

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: 9.23e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

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

May 03, 2023

The c.499A>G (p.S167G) alteration is located in exon 5 (coding exon 5) of the GLB1L3 gene. This alteration results from a A to G substitution at nucleotide position 499, causing the serine (S) at amino acid position 167 to be replaced by a glycine (G). 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	0.079
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	.;D
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Uncertain	0.27	D
MutationAssessor	Benign	0.83	L;L
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.073	T;T
Sift4G	Benign	0.092	T;T
Polyphen		0.090	B;B
Vest4		0.32
MutPred		0.89		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.44
MPC		0.059
ClinPred		0.071	T
GERP RS		2.1
Varity_R		0.11
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs760131354; hg19: chr11-134151986;