rs573009798

Variant names:

• chr11-94380325-G-C
• NM_016540.4:c.1096C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-94380325-G-C
• chr11-94380325-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016540.4(GPR83):​c.1096C>G​(p.Pro366Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,424 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P366T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPR83 NM_016540.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053554535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR83	NM_016540.4	c.1096C>G	p.Pro366Ala	missense_variant	Exon 4 of 4	ENST00000243673.7	NP_057624.3
GPR83	NM_001330345.2	c.970C>G	p.Pro324Ala	missense_variant	Exon 3 of 3		NP_001317274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR83	ENST00000243673.7	c.1096C>G	p.Pro366Ala	missense_variant	Exon 4 of 4	1	NM_016540.4	ENSP00000243673.2
GPR83	ENST00000539203.2	c.970C>G	p.Pro324Ala	missense_variant	Exon 3 of 3	5		ENSP00000441550.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460424 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726394

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	3.4
DANN	Benign	0.25
DEOGEN2	Benign	0.071	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.58	N;N
REVEL	Benign	0.095
Sift	Benign	0.79	T;T
Sift4G	Benign	0.76	T;T
Polyphen		0.0	B;.
Vest4		0.078
MutPred		0.29		Loss of glycosylation at P366 (P = 0.0044);.;
MVP		0.58
MPC		0.045
ClinPred		0.035	T
GERP RS		-0.85
Varity_R		0.054
gMVP		0.31

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: chr11-94113491;