Variant chr16-57680321-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000333493.9(ADGRG3):c.724A>T(p.Thr242Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000516 in 1,609,268 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

ADGRG3
ENST00000333493.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

Variant links:

Genes affected

ADGRG3 (HGNC:13728): (adhesion G protein-coupled receptor G3) Predicted to enable G protein-coupled receptor activity. Involved in G protein-coupled receptor signaling pathway and regulation of cell migration. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ADGRG3 links:

Genome browser will be placed here

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	Protein	UniProt
ADGRG3	NM_170776.5 linkuse as main transcript	c.724A>T	p.Thr242Ser	missense_variant	7/12	ENST00000333493.9	NP_740746.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADGRG3	ENST00000333493.9 linkuse as main transcript	c.724A>T	p.Thr242Ser	missense_variant	7/12	1	NM_170776.5	ENSP00000332900	P2
ADGRG3	ENST00000569977.1 linkuse as main transcript	n.115A>T		non_coding_transcript_exon_variant	2/6	1
ADGRG3	ENST00000567991.5 linkuse as main transcript	c.724A>T	p.Thr242Ser	missense_variant, NMD_transcript_variant	7/11	1		ENSP00000456409
ADGRG3	ENST00000450388.7 linkuse as main transcript	c.364A>T	p.Thr122Ser	missense_variant	6/11	2		ENSP00000404803	A2

Frequencies

GnomAD3 genomes

AF:

0.0000271

AC:

AN:

147524

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000984

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000448

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000151

AC:

AN:

251142

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135788

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:

0.000463

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000540

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

727184

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:

0.000412

Gnomad4 NFE exome

AF:

0.0000441

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000271

AC:

AN:

147524

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71796

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000984

Gnomad4 NFE

AF:

0.0000448

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

ExAC

AF:

0.000247

AC:

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

Jan 23, 2023

The c.724A>T (p.T242S) alteration is located in exon 7 (coding exon 7) of the ADGRG3 gene. This alteration results from a A to T substitution at nucleotide position 724, causing the threonine (T) at amino acid position 242 to be replaced by a serine (S). 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

0.38

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

D;D

Eigen

Benign

0.15

Eigen_PC

Benign

0.061

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.39

T;T

M_CAP

Uncertain

0.099

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Benign

-0.36

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.46

Sift

Benign

0.11

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.82

P;.

Vest4

0.69

MutPred

0.82

Gain of disorder (P = 0.072);.;

MVP

0.75

MPC

0.30

ClinPred

0.13

GERP RS

5.2

Varity_R

0.26

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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