rs1944671415

Variant names:

• chr11-94380241-C-G
• rs1944671415
• NM_016540.4:c.1180G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-94380241-C-G
• chr11-94380241-C-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.1180G>C​(p.Ala394Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 1,528,304 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. 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. A394V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: GPR83 NM_016540.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255
• 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=0.09378222).

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.1180G>C	p.Ala394Pro	missense	Exon 4 of 4	NP_057624.3
	GPR83	NM_001330345.2		c.1054G>C	p.Ala352Pro	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.1180G>C	p.Ala394Pro	missense	Exon 4 of 4	ENSP00000243673.2	Q9NYM4-1
	GPR83	ENST00000539203.2	TSL:5	c.1054G>C	p.Ala352Pro	missense	Exon 3 of 3	ENSP00000441550.1	Q9NYM4-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1376148 Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1 AN XY: 675452

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000327 AC: 1 AN: 30564

American (AMR) AF: 0.00 AC: 0 AN: 30992

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39030

South Asian (SAS) AF: 0.00 AC: 0 AN: 71302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5344

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071824

Other (OTH) AF: 0.00 AC: 0 AN: 56608

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74314

African (AFR) AF: 0.0000483 AC: 2 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.47
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	L
PhyloP100		0.26
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.11
Sift	Benign	0.29	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.052
MutPred		0.28		Gain of catalytic residue at A394 (P = 0.0432)
MVP		0.63
MPC		0.056
ClinPred		0.052	T
GERP RS		1.5
Varity_R		0.20
gMVP		0.48
Mutation Taster		=88/12	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: rs1944671415; hg19: chr11-94113407;