11-94380466-C-G

Position:

• chr11-94380466-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016540.4(GPR83):​c.955G>C​(p.Val319Leu) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR83 NM_016540.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56

Genes affected

GPR83 (HGNC:4523): (G protein-coupled receptor 83) Predicted to enable neuropeptide receptor activity. Predicted to be involved in neuropeptide signaling pathway. Predicted to act upstream of or within response to glucocorticoid. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12764567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR83	NM_016540.4	c.955G>C	p.Val319Leu	missense_variant	4/4	ENST00000243673.7	NP_057624.3
GPR83	NM_001330345.2	c.829G>C	p.Val277Leu	missense_variant	3/3		NP_001317274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR83	ENST00000243673.7	c.955G>C	p.Val319Leu	missense_variant	4/4	1	NM_016540.4	ENSP00000243673.2
GPR83	ENST00000539203.2	c.829G>C	p.Val277Leu	missense_variant	3/3	5		ENSP00000441550.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.955G>C (p.V319L) alteration is located in exon 4 (coding exon 4) of the GPR83 gene. This alteration results from a G to C substitution at nucleotide position 955, causing the valine (V) at amino acid position 319 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.83
DEOGEN2	Benign	0.10	T;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.018
Sift	Benign	0.14	T;T
Sift4G	Benign	0.68	T;T
Polyphen		0.087	B;.
Vest4		0.068
MutPred		0.31		Loss of methylation at K318 (P = 0.0693);.;
MVP		0.79
MPC		0.057
ClinPred		0.20	T
GERP RS		3.3
Varity_R		0.12
gMVP		0.41

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-94113632; COSMIC: COSV99704050;