2-132645474-A-T

Variant names:

• chr2-132645474-A-T
• rs1050940229
• NM_001508.3:c.1230A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001508.3(GPR39):​c.1230A>T​(p.Leu410Phe) 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. 14/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR39 NM_001508.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0320
• Publications: 0 publications found

Genes affected

GPR39 (HGNC:4496): (G protein-coupled receptor 39) This gene is a member of the ghrelin receptor family and encodes a rhodopsin-type G-protein-coupled receptor (GPCR). The encoded protein is involved in zinc-dependent signaling in epithelial tissue in intestines, prostate and salivary glands. The protein may also be involved in the pathophysiology of depression. [provided by RefSeq, Jun 2016]

LYPD1 (HGNC:28431): (LY6/PLAUR domain containing 1) Predicted to enable acetylcholine receptor binding activity and acetylcholine receptor inhibitor activity. Predicted to be involved in acetylcholine receptor signaling pathway. Predicted to act upstream of or within several processes, including behavioral fear response; cholinergic synaptic transmission; and negative regulation of protein localization to plasma membrane. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001508.3. 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
	GPR39	NM_001508.3	MANE Select	c.1230A>T	p.Leu410Phe	missense	Exon 2 of 2	NP_001499.1	O43194
	LYPD1	NM_144586.7	MANE Select	c.*571T>A		3_prime_UTR	Exon 3 of 3	NP_653187.3
	LYPD1	NM_001321234.2		c.*571T>A		3_prime_UTR	Exon 4 of 4	NP_001308163.1	Q8N2G4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR39	ENST00000329321.4	TSL:1 MANE Select	c.1230A>T	p.Leu410Phe	missense	Exon 2 of 2	ENSP00000327417.3	O43194
	LYPD1	ENST00000397463.3	TSL:1 MANE Select	c.*571T>A		3_prime_UTR	Exon 3 of 3	ENSP00000380605.2	Q8N2G4-1
	LYPD1	ENST00000892683.1		c.*571T>A		3_prime_UTR	Exon 2 of 2	ENSP00000562742.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.84
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.032
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.11
Sift	Benign	0.072	T
Sift4G	Uncertain	0.040	D
Polyphen		0.25	B
Vest4		0.38
MutPred		0.20		Gain of glycosylation at S411 (P = 0.0859)
MVP		0.60
MPC		1.1
ClinPred		0.14	T
GERP RS		-1.4
Varity_R		0.035
gMVP		0.32
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -17

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

Other links and lift over

dbSNP: rs1050940229; hg19: chr2-133403047;