NM_001370461.1:c.151G>T

Variant names:

• chr11-134342818-G-T
• NM_001370461.1:c.151G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370461.1(GLB1L2):​c.151G>T​(p.Gly51Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,728 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GLB1L2 NM_001370461.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.723
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41090772).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370461.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLB1L2	NM_001370461.1	MANE Select	c.151G>T	p.Gly51Cys	missense	Exon 2 of 19	NP_001357390.1	Q8IW92
	GLB1L2	NM_001370460.1		c.151G>T	p.Gly51Cys	missense	Exon 2 of 20	NP_001357389.1
	GLB1L2	NM_138342.4		c.151G>T	p.Gly51Cys	missense	Exon 2 of 20	NP_612351.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLB1L2	ENST00000535456.7	TSL:1 MANE Select	c.151G>T	p.Gly51Cys	missense	Exon 2 of 19	ENSP00000444628.1	Q8IW92
	GLB1L2	ENST00000855671.1		c.151G>T	p.Gly51Cys	missense	Exon 2 of 18	ENSP00000525730.1
	GLB1L2	ENST00000855672.1		c.87-4507G>T		intron	N/A	ENSP00000525731.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461728 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.44	D
MutationAssessor	Benign	1.7	L
PhyloP100		0.72
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.38
MutPred		0.56		Loss of sheet (P = 0.0126)
MVP		0.62
MPC		0.18
ClinPred		0.46	T
GERP RS		4.9
Varity_R		0.21
gMVP		0.82
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr11-134212712;