2-132645512-CC-GT

Variant names:

• chr2-132645512-CC-GT
• NM_001508.3:c.1268_1269delCCinsGT
• GPR39 p.Ser423Cys

Variant summary

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

The NM_001508.3(GPR39):​c.1268_1269delCCinsGT​(p.Ser423Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR39 NM_001508.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.748
• 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 0 ACMG points.

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.1268_1269delCCinsGT	p.Ser423Cys	missense	N/A	NP_001499.1	O43194
	LYPD1	NM_144586.7	MANE Select	c.*532_*533delGGinsAC		3_prime_UTR	Exon 3 of 3	NP_653187.3
	LYPD1	NM_001321234.2		c.*532_*533delGGinsAC		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.1268_1269delCCinsGT	p.Ser423Cys	missense	N/A	ENSP00000327417.3	O43194
	LYPD1	ENST00000397463.3	TSL:1 MANE Select	c.*532_*533delGGinsAC		3_prime_UTR	Exon 3 of 3	ENSP00000380605.2	Q8N2G4-1
	LYPD1	ENST00000892683.1		c.*532_*533delGGinsAC		3_prime_UTR	Exon 2 of 2	ENSP00000562742.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.75

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-133403085;