11-134332098-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001370461.1(GLB1L2):c.37A>G(p.Thr13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000932 in 1,590,332 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00048 (4 hom.)
• Consequence: GLB1L2 NM_001370461.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.166

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003944248).
• BP6: Variant 11-134332098-A-G is Benign according to our data. Variant chr11-134332098-A-G is described in ClinVar as [Benign]. Clinvar id is 717007.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00526 (798/151624) while in subpopulation AFR AF= 0.0186 (772/41406). AF 95% confidence interval is 0.0176. There are 4 homozygotes in gnomad4. There are 365 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLB1L2	NM_001370461.1	c.37A>G	p.Thr13Ala	missense_variant	1/19	ENST00000535456.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLB1L2	ENST00000535456.7	c.37A>G	p.Thr13Ala	missense_variant	1/19	1	NM_001370461.1	P1

Frequencies

GnomAD3 genomes AF: 0.00525 AC: 796 AN: 151512 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

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: 0.0000147

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00108 AC: 232 AN: 214202 Hom.: 0 AF XY: 0.000815 AC XY: 95 AN XY: 116580

Gnomad AFR exome AF: 0.0181

Gnomad AMR exome AF: 0.000386

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000104

Gnomad OTH exome AF: 0.000760

GnomAD4 exome AF: 0.000475 AC: 684 AN: 1438708 Hom.: 4 Cov.: 30 AF XY: 0.000399 AC XY: 285 AN XY: 714294

Gnomad4 AFR exome AF: 0.0189

Gnomad4 AMR exome AF: 0.000498

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000483

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000272

Gnomad4 OTH exome AF: 0.000892

GnomAD4 genome AF: 0.00526 AC: 798 AN: 151624 Hom.: 4 Cov.: 31 AF XY: 0.00493 AC XY: 365 AN XY: 74078

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.000891 Hom.: 1

Bravo AF: 0.00608

ESP6500AA AF: 0.0196 AC: 86

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00138 AC: 166

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 09, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	5.9
Dann	Benign	0.62
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.24	T;.
MetaRNN	Benign	0.0039	T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.77	N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.36	N;N
REVEL	Benign	0.18
Sift	Benign	0.29	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.0010	B;B
Vest4		0.056
MVP		0.20
MPC		0.23
ClinPred		0.0054	T
GERP RS		1.6
Varity_R		0.035
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs114706954; hg19: chr11-134201992;