Genetic Variant GLIPR1L1:p.Pro182Leu (chr12-75363125-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001304964.2(GLIPR1L1):c.545C>T(p.Pro182Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GLIPR1L1
NM_001304964.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

Variant links:

Genes affected

GLIPR1L1 (HGNC:28392): (GLIPR1 like 1) Predicted to be involved in single fertilization. Predicted to act upstream of or within binding activity of sperm to zona pellucida. Predicted to be located in sperm connecting piece. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

GLIPR1L1 links:

CAPS2 (HGNC:16471): (calcyphosine 2) Calcyphosine-2 is a calcium-binding protein with 2 EF-hand motifs (Wang et al., 2002 [PubMed 11846421]).[supplied by OMIM, Mar 2008]

CAPS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIPR1L1	NM_001304964.2 link	c.545C>T	p.Pro182Leu	missense_variant	Exon 4 of 6	ENST00000378695.9	NP_001291893.1	Q6UWM5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLIPR1L1	ENST00000378695.9 link	c.545C>T	p.Pro182Leu	missense_variant	Exon 4 of 6	1	NM_001304964.2	ENSP00000367967.4		Q6UWM5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1406118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698376

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.545C>T (p.P182L) alteration is located in exon 4 (coding exon 4) of the GLIPR1L1 gene. This alteration results from a C to T substitution at nucleotide position 545, causing the proline (P) at amino acid position 182 to be replaced by a leucine (L). 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

0.71

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;.

Eigen

Uncertain

0.40

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0093

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Benign

-0.38

MutationAssessor

Pathogenic

3.0

M;M

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.68

MutPred

0.68

Gain of catalytic residue at N179 (P = 0);Gain of catalytic residue at N179 (P = 0);

MVP

0.59

MPC

0.25

ClinPred

0.98

GERP RS

3.9

Varity_R

0.45

gMVP

0.86

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over