NM_016540.4:c.1181C>T

Variant names:

• chr11-94380240-G-A
• rs781580441
• NM_016540.4:c.1181C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016540.4(GPR83):​c.1181C>T​(p.Ala394Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000393 in 1,528,374 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A394T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: GPR83 NM_016540.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092576325).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016540.4. 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
	GPR83	NM_016540.4	MANE Select	c.1181C>T	p.Ala394Val	missense	Exon 4 of 4	NP_057624.3
	GPR83	NM_001330345.2		c.1055C>T	p.Ala352Val	missense	Exon 3 of 3	NP_001317274.1	Q9NYM4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR83	ENST00000243673.7	TSL:1 MANE Select	c.1181C>T	p.Ala394Val	missense	Exon 4 of 4	ENSP00000243673.2	Q9NYM4-1
	GPR83	ENST00000539203.2	TSL:5	c.1055C>T	p.Ala352Val	missense	Exon 3 of 3	ENSP00000441550.1	Q9NYM4-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000363 AC: 5 AN: 1376160 Hom.: 0 Cov.: 32 AF XY: 0.00000444 AC XY: 3 AN XY: 675448

African (AFR) AF: 0.0000654 AC: 2 AN: 30574

American (AMR) AF: 0.00 AC: 0 AN: 30994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20290

East Asian (EAS) AF: 0.00 AC: 0 AN: 39040

South Asian (SAS) AF: 0.00 AC: 0 AN: 71304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5348

European-Non Finnish (NFE) AF: 0.00000280 AC: 3 AN: 1071806

Other (OTH) AF: 0.00 AC: 0 AN: 56606

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.068
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.67
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.083
Sift	Benign	0.29	T
Sift4G	Benign	0.29	T
Polyphen		0.0010	B
Vest4		0.023
MutPred		0.18		Gain of MoRF binding (P = 0.1871)
MVP		0.64
MPC		0.046
ClinPred		0.051	T
GERP RS		0.67
Varity_R		0.035
gMVP		0.42
Mutation Taster		=92/8	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: rs781580441; hg19: chr11-94113406;