NM_001270396.2:c.221A>G

Variant names:

• chr12-75391337-A-G
• rs2045587125
• NM_001270396.2:c.221A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001270396.2(GLIPR1L2):​c.221A>G​(p.Asn74Ser) 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. 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: 1.33
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4169261).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270396.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIPR1L2	NM_001270396.2	MANE Select	c.221A>G	p.Asn74Ser	missense	Exon 1 of 6	NP_001257325.1	Q4G1C9-1
	GLIPR1L2	NM_152436.3		c.221A>G	p.Asn74Ser	missense	Exon 1 of 4	NP_689649.1	Q4G1C9-2
	GLIPR1L2	NR_072995.2		n.249A>G		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIPR1L2	ENST00000550916.6	TSL:1 MANE Select	c.221A>G	p.Asn74Ser	missense	Exon 1 of 6	ENSP00000448248.1	Q4G1C9-1
	GLIPR1L2	ENST00000320460.8	TSL:1	c.221A>G	p.Asn74Ser	missense	Exon 1 of 4	ENSP00000317385.4	Q4G1C9-2
	GLIPR1L2	ENST00000378692.7	TSL:1	c.-231A>G		5_prime_UTR	Exon 1 of 7	ENSP00000367963.3	Q4G1C9-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.053
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.35	B
Vest4		0.42
MutPred		0.68		Gain of catalytic residue at N74 (P = 0.0022)
MVP		0.24
MPC		0.15
ClinPred		0.96	D
GERP RS		1.4
PromoterAI		0.12	Neutral
Varity_R		0.27
gMVP		0.70
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2045587125; hg19: chr12-75785117;