12-75391285-T-A

Variant names:

• chr12-75391285-T-A
• rs773621549
• NM_001270396.2:c.169T>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001270396.2(GLIPR1L2):​c.169T>A​(p.Tyr57Asn) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y57H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLIPR1L2 NM_001270396.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

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.169T>A	p.Tyr57Asn	missense	Exon 1 of 6	NP_001257325.1	Q4G1C9-1
	GLIPR1L2	NM_152436.3		c.169T>A	p.Tyr57Asn	missense	Exon 1 of 4	NP_689649.1	Q4G1C9-2
	GLIPR1L2	NR_072995.2		n.197T>A		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.169T>A	p.Tyr57Asn	missense	Exon 1 of 6	ENSP00000448248.1	Q4G1C9-1
	GLIPR1L2	ENST00000320460.8	TSL:1	c.169T>A	p.Tyr57Asn	missense	Exon 1 of 4	ENSP00000317385.4	Q4G1C9-2
	GLIPR1L2	ENST00000378692.7	TSL:1	c.-283T>A		5_prime_UTR	Exon 1 of 7	ENSP00000367963.3	Q4G1C9-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.21
Sift	Benign	0.13	T
Sift4G	Uncertain	0.049	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.66		Gain of catalytic residue at Y57 (P = 0)
MVP		0.49
MPC		0.34
ClinPred		1.0	D
GERP RS		3.8
PromoterAI		-0.099	Neutral
Varity_R		0.58
gMVP		0.80
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs773621549; hg19: chr12-75785065;