11-94380201-T-A

Position:

• chr11-94380201-T-A

Variant summary

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

The NM_016540.4(GPR83):​c.1220A>T​(p.Gln407Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR83 NM_016540.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.43

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=0.207567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR83	NM_016540.4	c.1220A>T	p.Gln407Leu	missense_variant	4/4	ENST00000243673.7	NP_057624.3
GPR83	NM_001330345.2	c.1094A>T	p.Gln365Leu	missense_variant	3/3		NP_001317274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR83	ENST00000243673.7	c.1220A>T	p.Gln407Leu	missense_variant	4/4	1	NM_016540.4	ENSP00000243673.2
GPR83	ENST00000539203.2	c.1094A>T	p.Gln365Leu	missense_variant	3/3	5		ENSP00000441550.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Dec 26, 2023

The c.1220A>T (p.Q407L) alteration is located in exon 4 (coding exon 4) of the GPR83 gene. This alteration results from a A to T substitution at nucleotide position 1220, causing the glutamine (Q) at amino acid position 407 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	0.082
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.19
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.11
Sift	Benign	0.35	T;T
Sift4G	Benign	0.49	T;T
Polyphen		0.0	B;.
Vest4		0.30
MutPred		0.25		Loss of glycosylation at S408 (P = 0.0839);.;
MVP		0.79
MPC		0.046
ClinPred		0.46	T
GERP RS		4.7
Varity_R		0.088
gMVP		0.45

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: chr11-94113367;