Variant 12-75490511-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_006851.3(GLIPR1):c.526G>A(p.Gly176Arg) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GLIPR1
NM_006851.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.40

Variant links:

Genes affected

GLIPR1 (HGNC:17001): (GLI pathogenesis related 1) This gene encodes a protein with similarity to both the pathogenesis-related protein (PR) superfamily and the cysteine-rich secretory protein (CRISP) family. Increased expression of this gene is associated with myelomocytic differentiation in macrophage and decreased expression of this gene through gene methylation is associated with prostate cancer. The protein has proapoptotic activities in prostate and bladder cancer cells. This gene is a member of a cluster on chromosome 12 containing two other similar genes. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

GLIPR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLIPR1	NM_006851.3 linkuse as main transcript	c.526G>A	p.Gly176Arg	missense_variant	3/6	ENST00000266659.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLIPR1	ENST00000266659.8 linkuse as main transcript	c.526G>A	p.Gly176Arg	missense_variant	3/6	1	NM_006851.3	P1	P48060-1
GLIPR1	ENST00000456650.7 linkuse as main transcript	c.597G>A	p.Thr199=	synonymous_variant	4/6	1
GLIPR1	ENST00000550491.1 linkuse as main transcript	c.174G>A	p.Thr58=	synonymous_variant	3/4	3
GLIPR1	ENST00000536703.5 linkuse as main transcript	c.421-5066G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

130840

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246736

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133736

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000266

AC:

AN:

1126536

Hom.:

Cov.:

AF XY:

0.00000351

AC XY:

AN XY:

569564

show subpopulations

Gnomad4 AFR exome

AF:

0.0000382

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:

0.00000236

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

130840

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

61588

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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 22, 2023

The c.526G>A (p.G176R) alteration is located in exon 3 (coding exon 3) of the GLIPR1 gene. This alteration results from a G to A substitution at nucleotide position 526, causing the glycine (G) at amino acid position 176 to be replaced by an arginine (R). 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

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.29

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.054

MetaRNN

Pathogenic

0.87

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.41

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.81

MutPred

0.70

Gain of methylation at G176 (P = 0.0367);

MVP

0.82

MPC

0.70

ClinPred

0.99

GERP RS

5.6

Varity_R

0.97

gMVP

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over