Genetic Variant GLIPR1L1:p.Asp127Glu (chr12-75343899-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001304964.2(GLIPR1L1):c.381T>A(p.Asp127Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,459,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

GLIPR1L1
NM_001304964.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.30

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CAPS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049275428).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304964.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLIPR1L1	NM_001304964.2	MANE Select	c.381T>A	p.Asp127Glu	missense	Exon 2 of 6	NP_001291893.1	Q6UWM5-1
GLIPR1L1	NM_152779.4		c.381T>A	p.Asp127Glu	missense	Exon 2 of 5	NP_689992.1	Q6UWM5-2
CAPS2	NM_001355023.4		c.-29-17372A>T		intron	N/A	NP_001341952.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLIPR1L1	ENST00000378695.9	TSL:1 MANE Select	c.381T>A	p.Asp127Glu	missense	Exon 2 of 6	ENSP00000367967.4	Q6UWM5-1
GLIPR1L1	ENST00000312442.2	TSL:1	c.381T>A	p.Asp127Glu	missense	Exon 2 of 5	ENSP00000310770.2	Q6UWM5-2
CAPS2	ENST00000328705.7	TSL:1	n.*372-18611A>T		intron	N/A	ENSP00000331007.3	H7BXT1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

250996

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1459302

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726086

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39596

South Asian (SAS)

AF:

0.00

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.0000234

AC:

AN:

1110006

Other (OTH)

AF:

0.00

AC:

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.076

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.010

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.39

M_CAP

Benign

0.0065

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.52

PhyloP100

-1.3

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.63

REVEL

Benign

0.0030

Sift

Benign

0.40

Sift4G

Benign

0.57

Polyphen

0.0020

Vest4

0.072

MutPred

0.43

Gain of catalytic residue at Q122 (P = 0.034)

MVP

0.099

MPC

0.031

ClinPred

0.022

GERP RS

-1.0

Varity_R

0.065

gMVP

0.36

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over