Variant 4-22387778-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_145290.4(ADGRA3):c.3893A>C(p.Glu1298Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ADGRA3
NM_145290.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

Variant links:

Genes affected

ADGRA3 (HGNC:13839): (adhesion G protein-coupled receptor A3) This gene encodes a member of the G protein-coupled receptor superfamily. This membrane protein may play a role in tumor angiogenesis through its interaction with the human homolog of the Drosophila disc large tumor suppressor gene. This gene is mapped to a candidate region of chromosome 4 which may be associated with bipolar disorder and schizophrenia. [provided by RefSeq, Oct 2012]

ADGRA3 links:

ADGRA3 (HGNC:):

ADGRA3 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=0.1171343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRA3	NM_145290.4 linkuse as main transcript	c.3893A>C	p.Glu1298Ala	missense_variant	19/19	ENST00000334304.10	NP_660333.2	Q8IWK6-1
ADGRA3	XM_047449703.1 linkuse as main transcript	c.3302A>C	p.Glu1101Ala	missense_variant	19/19		XP_047305659.1
ADGRA3	XM_047449704.1 linkuse as main transcript	c.3302A>C	p.Glu1101Ala	missense_variant	19/19		XP_047305660.1
ADGRA3	XM_011513811.3 linkuse as main transcript	c.3215A>C	p.Glu1072Ala	missense_variant	14/14		XP_011512113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADGRA3	ENST00000334304.10 linkuse as main transcript	c.3893A>C	p.Glu1298Ala	missense_variant	19/19	1	NM_145290.4	ENSP00000334952.5	Q8IWK6-1
ADGRA3	ENST00000282943.9 linkuse as main transcript	n.3464A>C		non_coding_transcript_exon_variant	17/17	1
ADGRA3	ENST00000499527.6 linkuse as main transcript	n.3590A>C		non_coding_transcript_exon_variant	3/3	1
ADGRA3	ENST00000511051.5 linkuse as main transcript	n.104+1310A>C		intron_variant		3		ENSP00000424927.1	D6RER4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251300

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

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:

1461768

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinal dystrophy

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.52

Eigen

Benign

0.027

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

M_CAP

Benign

0.017

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.87

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.087

Sift

Benign

0.093

Sift4G

Benign

0.099

Polyphen

0.0010

Vest4

0.057

MutPred

0.41

Loss of solvent accessibility (P = 0.0404);

MVP

0.093

MPC

0.11

ClinPred

0.33

GERP RS

5.7

Varity_R

0.12

gMVP

0.082

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