Variant 11-134293164-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080407.3(GLB1L3):c.831G>T(p.Leu277Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

GLB1L3
NM_001080407.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.124

Variant links:

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 links:

GLB1L3 (HGNC:):

GLB1L3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03414634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLB1L3	NM_001080407.3 linkuse as main transcript	c.831G>T	p.Leu277Phe	missense_variant	9/20	ENST00000431683.7	NP_001073876.2	Q8NCI6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GLB1L3	ENST00000431683.7 linkuse as main transcript	c.831G>T	p.Leu277Phe	missense_variant	9/20	5	NM_001080407.3	ENSP00000396615.2	Q8NCI6-1
GLB1L3	ENST00000389887.9 linkuse as main transcript	c.831G>T	p.Leu277Phe	missense_variant	9/10	1		ENSP00000374537.5	Q8NCI6-4
GLB1L3	ENST00000486034.5 linkuse as main transcript	n.406G>T		non_coding_transcript_exon_variant	4/12	2
GLB1L3	ENST00000498012.5 linkuse as main transcript	n.1314G>T		non_coding_transcript_exon_variant	3/9	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249178

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135186

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000445

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461568

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.831G>T (p.L277F) alteration is located in exon 9 (coding exon 9) of the GLB1L3 gene. This alteration results from a G to T substitution at nucleotide position 831, causing the leucine (L) at amino acid position 277 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.20

CADD

Benign

3.1

DANN

Benign

0.098

DEOGEN2

Benign

0.28

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.034

T;T

MetaSVM

Uncertain

-0.11

MutationAssessor

Benign

-0.99

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.34

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0070

B;B

Vest4

0.096

MutPred

0.53

Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);

MVP

0.33

MPC

0.039

ClinPred

0.018

GERP RS

1.2

Varity_R

0.037

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over