Variant 16-57679190-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000333493.9(ADGRG3):c.506G>T(p.Gly169Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ADGRG3
ENST00000333493.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.187

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06607008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG3	NM_170776.5 linkuse as main transcript	c.506G>T	p.Gly169Val	missense_variant	5/12	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.506G>T	p.Gly169Val	missense_variant	5/12	1	NM_170776.5	ENSP00000332900	P2
ADGRG3	ENST00000567991.5 linkuse as main transcript	c.506G>T	p.Gly169Val	missense_variant, NMD_transcript_variant	5/11	1		ENSP00000456409
ADGRG3	ENST00000450388.7 linkuse as main transcript	c.146G>T	p.Gly49Val	missense_variant	4/11	2		ENSP00000404803	A2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152196

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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.506G>T (p.G169V) alteration is located in exon 5 (coding exon 5) of the ADGRG3 gene. This alteration results from a G to T substitution at nucleotide position 506, causing the glycine (G) at amino acid position 169 to be replaced by a valine (V). 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

0.096

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.9

DANN

Benign

0.87

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.066

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.99

N;N

REVEL

Benign

0.0080

Sift

Benign

0.49

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.22

B;.

Vest4

0.23

MutPred

0.45

Loss of disorder (P = 0.0396);.;

MVP

0.12

MPC

0.20

ClinPred

0.056

GERP RS

1.3

Varity_R

0.034

gMVP

0.44

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