12-75363125-C-T

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

6
3
10

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]
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]

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
GLIPR1L1NM_001304964.2 linkc.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
GLIPR1L1ENST00000378695.9 linkc.545C>T p.Pro182Leu missense_variant Exon 4 of 6 1 NM_001304964.2 ENSP00000367967.4 Q6UWM5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1406118
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
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.:
32

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
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;.
Eigen
Uncertain
0.40
Eigen_PC
Benign
0.22
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.64
T;T
M_CAP
Benign
0.0093
T
MetaRNN
Pathogenic
0.87
D;D
MetaSVM
Benign
-0.38
T
MutationAssessor
Pathogenic
3.0
M;M
PrimateAI
Benign
0.41
T
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
D
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.

Other links and lift over

hg19: chr12-75756905; API