Variant 12-75391348-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001270396.2(GLIPR1L2):c.232A>T(p.Met78Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,382 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GLIPR1L2
NM_001270396.2 missense, splice_region

Scores

Splicing: ADA: 0.9007

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

GLIPR1L2 (HGNC:28592): (GLIPR1 like 2) This gene encodes a member of the cysteine-rich secretory protein, antigen 5, and pathogenesis-related 1 superfamily. Members of this family have roles in a variety of processes, including cancer and immune defense. This gene is located in a cluster with two related genes on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

GLIPR1L2 links:

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ACMG classification

Classification made for transcript

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	UniProt
GLIPR1L2	NM_001270396.2 linkuse as main transcript	c.232A>T	p.Met78Leu	missense_variant, splice_region_variant	1/6	ENST00000550916.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLIPR1L2	ENST00000550916.6 linkuse as main transcript	c.232A>T	p.Met78Leu	missense_variant, splice_region_variant	1/6	1	NM_001270396.2	P1	Q4G1C9-1
GLIPR1L2	ENST00000320460.8 linkuse as main transcript	c.232A>T	p.Met78Leu	missense_variant, splice_region_variant	1/4	1			Q4G1C9-2
GLIPR1L2	ENST00000378692.7 linkuse as main transcript	c.-220A>T		splice_region_variant, 5_prime_UTR_variant	1/7	1			Q4G1C9-5
GLIPR1L2	ENST00000547164.1 linkuse as main transcript	c.232A>T	p.Met78Leu	missense_variant, splice_region_variant	1/3	5			Q4G1C9-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461382

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727068

show subpopulations

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Oct 25, 2023

The c.232A>T (p.M78L) alteration is located in exon 1 (coding exon 1) of the GLIPR1L2 gene. This alteration results from a A to T substitution at nucleotide position 232, causing the methionine (M) at amino acid position 78 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

Uncertain

0.45

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.048

T;.;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.0094

MetaRNN

Uncertain

0.72

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;L

MutationTaster

Benign

0.95

D;D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.7

D;N;N

REVEL

Benign

0.18

Sift

Benign

0.036

D;D;D

Sift4G

Pathogenic

0.0010

D;T;D

Polyphen

0.95

P;P;.

Vest4

0.63

MutPred

0.70

Gain of catalytic residue at M78 (P = 3e-04);Gain of catalytic residue at M78 (P = 3e-04);Gain of catalytic residue at M78 (P = 3e-04);

MVP

0.37

MPC

0.15

ClinPred

0.99

GERP RS

3.8

Varity_R

0.63

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.90

dbscSNV1_RF

Benign

0.52

SpliceAI score (max)

0.13

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