12-75490490-G-A

Position:

• chr12-75490490-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006851.3(GLIPR1):​c.505G>A​(p.Ala169Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000156 in 1,280,874 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: GLIPR1 NM_006851.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIPR1	NM_006851.3	c.505G>A	p.Ala169Thr	missense_variant	3/6	ENST00000266659.8	NP_006842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLIPR1	ENST00000266659.8	c.505G>A	p.Ala169Thr	missense_variant	3/6	1	NM_006851.3	ENSP00000266659.3
GLIPR1	ENST00000456650.7	c.576G>A	p.Glu192Glu	synonymous_variant	4/6	1		ENSP00000391144.3
GLIPR1	ENST00000550491.1	c.153G>A	p.Glu51Glu	synonymous_variant	3/4	3		ENSP00000448008.1
GLIPR1	ENST00000536703.5	n.421-5087G>A		intron_variant		2		ENSP00000440595.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000156 AC: 2 AN: 1280874 Hom.: 0 Cov.: 27 AF XY: 0.00000157 AC XY: 1 AN XY: 637750

Gnomad4 AFR exome AF: 0.00

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: 0.00000201

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.505G>A (p.A169T) 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 505, causing the alanine (A) at amino acid position 169 to be replaced by a threonine (T). 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	0.27
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.020	D
Polyphen		0.99	D
Vest4		0.31
MutPred		0.59		Gain of sheet (P = 0.0827);
MVP		0.26
MPC		0.63
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.68
gMVP		0.52

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

Other links and lift over

dbSNP: rs1209546456; hg19: chr12-75884270;