Variant 6-68956114-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001704.3(ADGRB3):c.1286C>A(p.Ala429Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ADGRB3
NM_001704.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.90

Variant links:

Genes affected

ADGRB3 (HGNC:945): (adhesion G protein-coupled receptor B3) This p53-target gene encodes a brain-specific angiogenesis inhibitor, a seven-span transmembrane protein, and is thought to be a member of the secretin receptor family. Brain-specific angiogenesis proteins BAI2 and BAI3 are similar to BAI1 in structure, have similar tissue specificities, and may also play a role in angiogenesis. [provided by RefSeq, Jul 2008]

ADGRB3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRB3	NM_001704.3 linkuse as main transcript	c.1286C>A	p.Ala429Glu	missense_variant	7/32	ENST00000370598.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRB3	ENST00000370598.6 linkuse as main transcript	c.1286C>A	p.Ala429Glu	missense_variant	7/32	1	NM_001704.3	P1	O60242-1
ADGRB3	ENST00000546190.5 linkuse as main transcript	c.1286C>A	p.Ala429Glu	missense_variant	5/30	1		P1	O60242-1
ADGRB3	ENST00000684661.1 linkuse as main transcript	c.1286C>A	p.Ala429Glu	missense_variant, NMD_transcript_variant	7/32

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250736

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135494

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Feb 07, 2023

The c.1286C>A (p.A429E) alteration is located in exon 7 (coding exon 5) of the ADGRB3 gene. This alteration results from a C to A substitution at nucleotide position 1286, causing the alanine (A) at amino acid position 429 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.34

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Benign

0.062

T;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.13

Sift

Benign

0.061

T;.

Sift4G

Benign

0.076

T;T

Polyphen

0.84

P;P

Vest4

0.66

MutPred

0.57

Loss of MoRF binding (P = 0.074);Loss of MoRF binding (P = 0.074);

MVP

0.043

MPC

0.62

ClinPred

0.66

GERP RS

5.7

Varity_R

0.25

gMVP

0.53

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