chr12-75391337-A-G

Position:

• chr12-75391337-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLIPR1L2	NM_001270396.2	c.221A>G	p.Asn74Ser	missense_variant	1/6	ENST00000550916.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLIPR1L2	ENST00000550916.6	c.221A>G	p.Asn74Ser	missense_variant	1/6	1	NM_001270396.2	P1
GLIPR1L2	ENST00000320460.8	c.221A>G	p.Asn74Ser	missense_variant	1/4	1
GLIPR1L2	ENST00000378692.7	c.-231A>G		5_prime_UTR_variant	1/7	1
GLIPR1L2	ENST00000547164.1	c.221A>G	p.Asn74Ser	missense_variant	1/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M;M
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Benign	0.053
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0040	D;D;T
Polyphen		0.35	B;D;.
Vest4		0.42
MutPred		0.68		Gain of catalytic residue at N74 (P = 0.0022);Gain of catalytic residue at N74 (P = 0.0022);Gain of catalytic residue at N74 (P = 0.0022);
MVP		0.24
MPC		0.15
ClinPred		0.96	D
GERP RS		1.4
Varity_R		0.27
gMVP		0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs2045587125; hg19: chr12-75785117;