Variant chr12-75490493-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006851.3(GLIPR1):c.508C>T(p.His170Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000093 in 1,333,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

GLIPR1
NM_006851.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4057367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIPR1	NM_006851.3 linkuse as main transcript	c.508C>T	p.His170Tyr	missense_variant	3/6	ENST00000266659.8	NP_006842.2	P48060-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GLIPR1	ENST00000266659.8 linkuse as main transcript	c.508C>T	p.His170Tyr	missense_variant	3/6	1	NM_006851.3	ENSP00000266659.3	P48060-1
GLIPR1	ENST00000456650.7 linkuse as main transcript	c.579C>T	p.His193His	synonymous_variant	4/6	1		ENSP00000391144.3	F6VVE8
GLIPR1	ENST00000550491.1 linkuse as main transcript	c.156C>T	p.His52His	synonymous_variant	3/4	3		ENSP00000448008.1	J3QTC9
GLIPR1	ENST00000536703.5 linkuse as main transcript	n.421-5084C>T		intron_variant		2		ENSP00000440595.1	B4E3S5

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

119544

Hom.:

Cov.:

show subpopulations

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:

0.000177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000559

AC:

AN:

250340

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135396

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:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000930

AC:

113

AN:

1214452

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

604872

show subpopulations

Gnomad4 AFR exome

AF:

0.0000378

Gnomad4 AMR exome

AF:

0.0000263

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:

0.000116

Gnomad4 OTH exome

AF:

0.0000221

GnomAD4 genome

AF:

0.0000920

AC:

AN:

119544

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

54754

show subpopulations

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:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000149

Hom.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

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

Nov 19, 2022

The c.508C>T (p.H170Y) alteration is located in exon 3 (coding exon 3) of the GLIPR1 gene. This alteration results from a C to T substitution at nucleotide position 508, causing the histidine (H) at amino acid position 170 to be replaced by a tyrosine (Y). 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

Benign

0.29

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

0.048

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0079

MetaRNN

Benign

0.41

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.15

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.1

REVEL

Benign

0.20

Sift

Benign

0.13

Sift4G

Benign

0.28

Polyphen

1.0

Vest4

0.59

MutPred

0.57

Loss of catalytic residue at H170 (P = 0.1239);

MVP

0.12

MPC

0.68

ClinPred

0.45

GERP RS

3.7

Varity_R

0.40

gMVP

0.54

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

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