chr19-14625581-T-C

Position:

chr19-14625581-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032571.5(ADGRE3):c.1831A>G(p.Lys611Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,612,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ADGRE3
NM_032571.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.19144002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRE3	NM_032571.5 linkuse as main transcript	c.1831A>G	p.Lys611Glu	missense_variant	15/16	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.1831A>G	p.Lys611Glu	missense_variant	15/16	1	NM_032571.5	ENSP00000253673	P1	Q9BY15-1
ADGRE3	ENST00000344373.8 linkuse as main transcript	c.1675A>G	p.Lys559Glu	missense_variant	14/15	1		ENSP00000340758		Q9BY15-2
ADGRE3	ENST00000443157.6 linkuse as main transcript	c.1453A>G	p.Lys485Glu	missense_variant	12/13	2		ENSP00000396208
ADGRE3	ENST00000599900.5 linkuse as main transcript	c.1186A>G	p.Lys396Glu	missense_variant	14/15	5		ENSP00000471853

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000147

AC:

AN:

250944

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000174

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:

0.000247

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000167

AC:

244

AN:

1460166

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

119

AN XY:

726462

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000112

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000211

Hom.:

Bravo

AF:

0.000121

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

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

Aug 11, 2022

The c.1831A>G (p.K611E) alteration is located in exon 15 (coding exon 15) of the ADGRE3 gene. This alteration results from a A to G substitution at nucleotide position 1831, causing the lysine (K) at amino acid position 611 to be replaced by a glutamic acid (E). 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

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.056

.;.;.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.56

T;T;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.1

D;D;.;D

REVEL

Benign

0.048

Sift

Uncertain

0.0050

D;D;.;D

Sift4G

Uncertain

0.012

D;D;D;D

Polyphen

0.86

P;D;.;P

Vest4

0.46

MVP

0.17

MPC

0.25

ClinPred

0.12

GERP RS

2.6

Varity_R

0.30

gMVP

0.20

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

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