Variant 19-14630148-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032571.5(ADGRE3):c.1703G>A(p.Gly568Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

ADGRE3
NM_032571.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.64

Variant links:

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]

ADGRE3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.929

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRE3	NM_032571.5 linkuse as main transcript	c.1703G>A	p.Gly568Asp	missense_variant	14/16	ENST00000253673.6	NP_115960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRE3	ENST00000253673.6 linkuse as main transcript	c.1703G>A	p.Gly568Asp	missense_variant	14/16	1	NM_032571.5	ENSP00000253673	P1	Q9BY15-1
ADGRE3	ENST00000344373.8 linkuse as main transcript	c.1547G>A	p.Gly516Asp	missense_variant	13/15	1		ENSP00000340758		Q9BY15-2
ADGRE3	ENST00000443157.6 linkuse as main transcript	c.1325G>A	p.Gly442Asp	missense_variant	11/13	2		ENSP00000396208
ADGRE3	ENST00000599900.5 linkuse as main transcript	c.1058G>A	p.Gly353Asp	missense_variant	13/15	5		ENSP00000471853

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD3 exomes

AF:

0.0000917

AC:

AN:

250954

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1461212

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000622

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.0000548

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.1703G>A (p.G568D) alteration is located in exon 14 (coding exon 14) of the ADGRE3 gene. This alteration results from a G to A substitution at nucleotide position 1703, causing the glycine (G) at amino acid position 568 to be replaced by an aspartic acid (D). 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

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

.;.;.;T

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Benign

0.065

MetaRNN

Pathogenic

0.93

D;D;D;D

MetaSVM

Uncertain

0.41

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.1

D;D;.;D

REVEL

Uncertain

0.51

Sift

Uncertain

0.0010

D;D;.;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.90

MVP

0.60

MPC

0.71

ClinPred

0.98

GERP RS

3.8

Varity_R

0.92

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over