11-134332098-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370461.1(GLB1L2):​c.37A>C​(p.Thr13Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,438,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11378485).

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>C	p.Thr13Pro	missense	Exon 1 of 19	NP_001357390.1	Q8IW92
	GLB1L2	NM_001370460.1		c.37A>C	p.Thr13Pro	missense	Exon 1 of 20	NP_001357389.1
	GLB1L2	NM_138342.4		c.37A>C	p.Thr13Pro	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>C	p.Thr13Pro	missense	Exon 1 of 19	ENSP00000444628.1	Q8IW92
	GLB1L2	ENST00000855671.1		c.37A>C	p.Thr13Pro	missense	Exon 1 of 18	ENSP00000525730.1
	GLB1L2	ENST00000855672.1		c.37A>C	p.Thr13Pro	missense	Exon 1 of 16	ENSP00000525731.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000467 AC: 1 AN: 214202 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000104

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438712 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 714298

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

American (AMR) AF: 0.00 AC: 0 AN: 42142

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

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

South Asian (SAS) AF: 0.00 AC: 0 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: 9.07e-7 AC: 1 AN: 1102592

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.11	T
MetaSVM	Uncertain	0.10	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.17
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.14	N
REVEL	Uncertain	0.40
Sift	Benign	0.064	T
Sift4G	Benign	0.22	T
Polyphen		0.17	B
Vest4		0.33
MutPred		0.54		Gain of loop (P = 0.0045)
MVP		0.20
MPC		0.44
ClinPred		0.088	T
GERP RS		1.6
PromoterAI		-0.012	Neutral
Varity_R		0.091
gMVP		0.73
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs114706954; hg19: chr11-134201992;