chr7-113083670-C-T

Position:

• chr7-113083670-C-T

Variant summary

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

The NM_001146267.2(GPR85):​c.1052G>A​(p.Ser351Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: GPR85 NM_001146267.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.98

Genes affected

GPR85 (HGNC:4536): (G protein-coupled receptor 85) Members of the G protein-coupled receptor (GPCR) family, such as GPR85, have a similar structure characterized by 7 transmembrane domains. Activation of GPCRs by extracellular stimuli, such as neurotransmitters, hormones, or light, induces an intracellular signaling cascade mediated by heterotrimeric GTP-binding proteins, or G proteins (Matsumoto et al., 2000 [PubMed 10833454]).[supplied by OMIM, Aug 2008]

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=0.23102415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR85	NM_001146267.2	c.1052G>A	p.Ser351Asn	missense_variant	3/3	ENST00000424100.2	NP_001139739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR85	ENST00000424100.2	c.1052G>A	p.Ser351Asn	missense_variant	3/3	1	NM_001146267.2	ENSP00000396763.1
GPR85	ENST00000297146.7	c.1052G>A	p.Ser351Asn	missense_variant	3/3	1		ENSP00000297146.2
GPR85	ENST00000449591.2	c.1052G>A	p.Ser351Asn	missense_variant	2/2	1		ENSP00000401178.1
GPR85	ENST00000610164.1	n.1052G>A		non_coding_transcript_exon_variant	2/3	5		ENSP00000476863.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jul 09, 2024

The c.1052G>A (p.S351N) alteration is located in exon 3 (coding exon 1) of the GPR85 gene. This alteration results from a G to A substitution at nucleotide position 1052, causing the serine (S) at amino acid position 351 to be replaced by an asparagine (N). 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	0.22
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;T;T
Eigen	Benign	0.039
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	.;.;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.040	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.43	B;B;B
Vest4		0.47
MutPred		0.40		Loss of catalytic residue at S351 (P = 0.0031);Loss of catalytic residue at S351 (P = 0.0031);Loss of catalytic residue at S351 (P = 0.0031);
MVP		0.082
MPC		0.59
ClinPred		0.62	D
GERP RS		4.9
Varity_R		0.27
gMVP		0.68

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: chr7-112723725;