Variant 11-134292201-C-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.799C>T(p.His267Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,459,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000048 ( 0 hom. )

Consequence

GLB1L3
NM_001080407.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.719

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:

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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=0.053276896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLB1L3	NM_001080407.3 linkuse as main transcript	c.799C>T	p.His267Tyr	missense_variant	8/20	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.799C>T	p.His267Tyr	missense_variant	8/20	5	NM_001080407.3	ENSP00000396615.2	Q8NCI6-1
GLB1L3	ENST00000389887.9 linkuse as main transcript	c.799C>T	p.His267Tyr	missense_variant	8/10	1		ENSP00000374537.5	Q8NCI6-4
GLB1L3	ENST00000486034.5 linkuse as main transcript	n.374C>T		non_coding_transcript_exon_variant	3/12	2
GLB1L3	ENST00000498012.5 linkuse as main transcript	n.351C>T		non_coding_transcript_exon_variant	3/9	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1459830

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726304

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 16, 2023

The c.799C>T (p.H267Y) alteration is located in exon 8 (coding exon 8) of the GLB1L3 gene. This alteration results from a C to T substitution at nucleotide position 799, causing the histidine (H) at amino acid position 267 to be replaced by a tyrosine (Y). 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

0.076

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.090

DANN

Benign

0.22

DEOGEN2

Benign

0.35

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.053

T;T

MetaSVM

Uncertain

0.034

MutationAssessor

Benign

0.33

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.22

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.12

MutPred

0.64

Loss of disorder (P = 0.0389);Loss of disorder (P = 0.0389);

MVP

0.26

MPC

0.041

ClinPred

0.021

GERP RS

-4.3

Varity_R

0.029

gMVP

0.58

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over