chr2-132645391-G-A

Variant names:

• chr2-132645391-G-A
• rs559802992
• NM_001508.3:c.1147G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001508.3(GPR39):​c.1147G>A​(p.Asp383Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign 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. D383G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPR39 NM_001508.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06771439).

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.1147G>A	p.Asp383Asn	missense	Exon 2 of 2	NP_001499.1	O43194
	LYPD1	NM_144586.7	MANE Select	c.*654C>T		3_prime_UTR	Exon 3 of 3	NP_653187.3
	LYPD1	NM_001321234.2		c.*654C>T		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.1147G>A	p.Asp383Asn	missense	Exon 2 of 2	ENSP00000327417.3	O43194
	LYPD1	ENST00000397463.3	TSL:1 MANE Select	c.*654C>T		3_prime_UTR	Exon 3 of 3	ENSP00000380605.2	Q8N2G4-1
	LYPD1	ENST00000892683.1		c.*654C>T		3_prime_UTR	Exon 2 of 2	ENSP00000562742.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461386 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727000

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.4
DANN	Benign	0.95
DEOGEN2	Benign	0.078	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.51
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.13
Sift	Benign	0.32	T
Sift4G	Benign	0.49	T
Polyphen		0.0030	B
Vest4		0.049
MutPred		0.19		Gain of MoRF binding (P = 0.0418)
MVP		0.57
MPC		0.31
ClinPred		0.080	T
GERP RS		0.56
Varity_R		0.017
gMVP		0.23
Mutation Taster		=96/4	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: rs559802992; hg19: chr2-133402964; COSMIC: COSV61416803; COSMIC: COSV61416803;