rs45508602

Variant names:

• chr19-14641513-C-G
• rs45508602
• NM_032571.5:c.1154G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-14641513-C-G
• chr19-14641513-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032571.5(ADGRE3):​c.1154G>C​(p.Arg385Pro) 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. 13/21 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: 31)
• Consequence: ADGRE3 NM_032571.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 19 publications found

Genes affected

ADGRE3 (HGNC:23647): (adhesion G protein-coupled receptor E3) This gene encodes a member of the class B seven-span transmembrane (TM7) receptor family expressed predominantly by cells of the immune system. Family members are characterized by an extended extracellular region with a variable number of N-terminal epidermal growth factor (EGF)-like domains coupled to a TM7 domain via a mucin-like spacer domain. This gene is closely linked to the gene encoding egf-like molecule containing mucin-like hormone receptor 2 on chromosome 19. This protein may play a role in myeloid-myeloid interactions during immune and inflammatory responses. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37559837).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032571.5. 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
	ADGRE3	NM_032571.5	MANE Select	c.1154G>C	p.Arg385Pro	missense	Exon 10 of 16	NP_115960.2	Q9BY15-1
	ADGRE3	NM_001289158.2		c.998G>C	p.Arg333Pro	missense	Exon 9 of 15	NP_001276087.1	Q9BY15-2
	ADGRE3	NM_001289159.2		c.776G>C	p.Arg259Pro	missense	Exon 7 of 13	NP_001276088.1	E7EW83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRE3	ENST00000253673.6	TSL:1 MANE Select	c.1154G>C	p.Arg385Pro	missense	Exon 10 of 16	ENSP00000253673.4	Q9BY15-1
	ADGRE3	ENST00000344373.8	TSL:1	c.998G>C	p.Arg333Pro	missense	Exon 9 of 15	ENSP00000340758.4	Q9BY15-2
	ADGRE3	ENST00000718247.1		c.1154G>C	p.Arg385Pro	missense	Exon 10 of 16	ENSP00000520692.1	A0ABB0MV84

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.76	T
PhyloP100		2.0
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.52	P
Vest4		0.34
MutPred		0.76		Loss of helix (P = 0.0093)
MVP		0.30
MPC		0.33
ClinPred		0.83	D
GERP RS		2.8
Varity_R		0.56
gMVP		0.77
Mutation Taster		=90/10	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: rs45508602; hg19: chr19-14752325;