NM_001508.3:c.1268C>G

Variant names:

• chr2-132645512-C-G
• rs61757692
• NM_001508.3:c.1268C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001508.3(GPR39):​c.1268C>G​(p.Ser423Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,612,956 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (9 hom.)
• Consequence: GPR39 NM_001508.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.748
• Publications: 5 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008588046).
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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.1268C>G	p.Ser423Cys	missense	Exon 2 of 2	NP_001499.1	O43194
	LYPD1	NM_144586.7	MANE Select	c.*533G>C		3_prime_UTR	Exon 3 of 3	NP_653187.3
	LYPD1	NM_001321234.2		c.*533G>C		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.1268C>G	p.Ser423Cys	missense	Exon 2 of 2	ENSP00000327417.3	O43194
	LYPD1	ENST00000397463.3	TSL:1 MANE Select	c.*533G>C		3_prime_UTR	Exon 3 of 3	ENSP00000380605.2	Q8N2G4-1
	LYPD1	ENST00000892683.1		c.*533G>C		3_prime_UTR	Exon 2 of 2	ENSP00000562742.1

Frequencies

GnomAD3 genomes AF: 0.00169 AC: 256 AN: 151918 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000558

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.00137 AC: 340 AN: 248976 AF XY: 0.00148

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00148

Gnomad NFE exome AF: 0.00214

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00235 AC: 3431 AN: 1460920 Hom.: 9 Cov.: 32 AF XY: 0.00237 AC XY: 1719 AN XY: 726836

African (AFR) AF: 0.000455 AC: 15 AN: 32944

American (AMR) AF: 0.000604 AC: 27 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26078

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.00107 AC: 92 AN: 86246

European-Finnish (FIN) AF: 0.00110 AC: 59 AN: 53410

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.00280 AC: 3111 AN: 1111758

Other (OTH) AF: 0.00197 AC: 119 AN: 60318

GnomAD4 genome AF: 0.00168 AC: 256 AN: 152036 Hom.: 0 Cov.: 33 AF XY: 0.00149 AC XY: 111 AN XY: 74352

African (AFR) AF: 0.000556 AC: 23 AN: 41342

American (AMR) AF: 0.000523 AC: 8 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4826

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00303 AC: 206 AN: 68018

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00252 Hom.: 0

Bravo AF: 0.00139

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00363 AC: 14

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00267 AC: 23

ExAC AF: 0.00133 AC: 161

Asia WGS AF: 0.000289 AC: 2 AN: 3478

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	0.082
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.75
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.067
Sift	Benign	0.089	T
Sift4G	Benign	0.095	T
Polyphen		0.33	B
Vest4		0.14
MVP		0.68
MPC		0.39
ClinPred		0.0060	T
GERP RS		4.3
Varity_R		0.039
gMVP		0.32
Mutation Taster		=84/16	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: rs61757692; hg19: chr2-133403085; COSMIC: COSV107341385; COSMIC: COSV107341385;