11-134332098-A-T

Variant names:

• chr11-134332098-A-T
• rs114706954
• NM_001370461.1:c.37A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001370461.1(GLB1L2):​c.37A>T​(p.Thr13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000283 in 1,590,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T13A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: GLB1L2 NM_001370461.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034591228).

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.37A>T	p.Thr13Ser	missense	Exon 1 of 19	NP_001357390.1	Q8IW92
	GLB1L2	NM_001370460.1		c.37A>T	p.Thr13Ser	missense	Exon 1 of 20	NP_001357389.1
	GLB1L2	NM_138342.4		c.37A>T	p.Thr13Ser	missense	Exon 1 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.37A>T	p.Thr13Ser	missense	Exon 1 of 19	ENSP00000444628.1	Q8IW92
	GLB1L2	ENST00000855671.1		c.37A>T	p.Thr13Ser	missense	Exon 1 of 18	ENSP00000525730.1
	GLB1L2	ENST00000855672.1		c.37A>T	p.Thr13Ser	missense	Exon 1 of 16	ENSP00000525731.1

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151514 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.000135 AC: 29 AN: 214202 AF XY: 0.000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000901

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000278 AC: 40 AN: 1438710 Hom.: 0 Cov.: 30 AF XY: 0.0000238 AC XY: 17 AN XY: 714296

African (AFR) AF: 0.00 AC: 0 AN: 31960

American (AMR) AF: 0.000925 AC: 39 AN: 42140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25584

East Asian (EAS) AF: 0.00 AC: 0 AN: 38052

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4860

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102592

Other (OTH) AF: 0.00 AC: 0 AN: 59412

GnomAD4 genome AF: 0.0000330 AC: 5 AN: 151626 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74078

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.000327 AC: 5 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5034

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67796

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.0000718

ExAC AF: 0.00000834 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	7.4
DANN	Benign	0.67
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.035	T
MetaSVM	Uncertain	-0.090	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.17
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.20
Sift	Benign	0.058	T
Sift4G	Benign	0.43	T
Polyphen		0.020	B
Vest4		0.14
MutPred		0.37		Loss of helix (P = 0.0558)
MVP		0.23
MPC		0.25
ClinPred		0.019	T
GERP RS		1.6
PromoterAI		0.033	Neutral
Varity_R		0.034
gMVP		0.62
Mutation Taster		=98/2	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

dbSNP: rs114706954; hg19: chr11-134201992;