12-75391181-G-T

Variant names:

• chr12-75391181-G-T
• rs1485169630
• NM_001270396.2:c.65G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270396.2(GLIPR1L2):​c.65G>T​(p.Gly22Val) 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 benign outcome for this variant. 15/21 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)
• Consequence: GLIPR1L2 NM_001270396.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0260

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07893166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIPR1L2	NM_001270396.2	c.65G>T	p.Gly22Val	missense_variant	Exon 1 of 6	ENST00000550916.6	NP_001257325.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLIPR1L2	ENST00000550916.6	c.65G>T	p.Gly22Val	missense_variant	Exon 1 of 6	1	NM_001270396.2	ENSP00000448248.1
GLIPR1L2	ENST00000320460.8	c.65G>T	p.Gly22Val	missense_variant	Exon 1 of 4	1		ENSP00000317385.4
GLIPR1L2	ENST00000378692	c.-387G>T		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000367963.3
GLIPR1L2	ENST00000547164.1	c.65G>T	p.Gly22Val	missense_variant	Exon 1 of 3	5		ENSP00000447980.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.65G>T (p.G22V) alteration is located in exon 1 (coding exon 1) of the GLIPR1L2 gene. This alteration results from a G to T substitution at nucleotide position 65, causing the glycine (G) at amino acid position 22 to be replaced by a valine (V). 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	0.093
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.87
DEOGEN2	Benign	0.0061	T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.42	T;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.079	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.81	L;L;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.030	N;N;N
REVEL	Benign	0.039
Sift	Benign	0.13	T;T;T
Sift4G	Uncertain	0.056	T;T;D
Polyphen		0.0070	B;B;.
Vest4		0.14
MutPred		0.61		Gain of catalytic residue at G21 (P = 0.001);Gain of catalytic residue at G21 (P = 0.001);Gain of catalytic residue at G21 (P = 0.001);
MVP		0.076
MPC		0.047
ClinPred		0.097	T
GERP RS		-3.1
Varity_R		0.028
gMVP		0.51

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: rs1485169630; hg19: chr12-75784961;