Variant 3-100637386-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 NM_032787.3(ADGRG7):c.682G>T(p.Asp228Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,612,412 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 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

ADGRG7
NM_032787.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.374

Variant links:

Genes affected

ADGRG7 (HGNC:19241): (adhesion G protein-coupled receptor G7) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ADGRG7 links:

ADGRG7 (HGNC:):

ADGRG7 links:

Genome browser will be placed here

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=0.06219521).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG7	NM_032787.3 linkuse as main transcript	c.682G>T	p.Asp228Tyr	missense_variant	6/16	ENST00000273352.8	NP_116176.2	Q96K78Q6ZMH4
ADGRG7	NM_001308362.1 linkuse as main transcript	c.45G>T	p.Met15Ile	missense_variant	2/10		NP_001295291.1	E9PHI0Q6ZMH4B7Z303
ADGRG7	XM_047449088.1 linkuse as main transcript	c.277G>T	p.Asp93Tyr	missense_variant	4/14		XP_047305044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADGRG7	ENST00000273352.8 linkuse as main transcript	c.682G>T	p.Asp228Tyr	missense_variant	6/16	1	NM_032787.3	ENSP00000273352.3	Q96K78
ADGRG7	ENST00000475887.1 linkuse as main transcript	c.45G>T	p.Met15Ile	missense_variant	2/10	2		ENSP00000419788.1	E9PHI0
ADGRG7	ENST00000481361.1 linkuse as main transcript	n.374G>T		non_coding_transcript_exon_variant	2/4	4
ADGRG7	ENST00000493081.1 linkuse as main transcript	n.372G>T		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152206

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000108

AC:

AN:

251010

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.0000464

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000740

AC:

108

AN:

1460206

Hom.:

Cov.:

AF XY:

0.0000729

AC XY:

AN XY:

726566

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000563

Gnomad4 NFE exome

AF:

0.0000900

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74360

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:

0.0000941

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000967

Hom.:

Bravo

AF:

0.0000491

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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

Dec 17, 2023

The c.682G>T (p.D228Y) alteration is located in exon 6 (coding exon 6) of the ADGRG7 gene. This alteration results from a G to T substitution at nucleotide position 682, causing the aspartic acid (D) at amino acid position 228 to be replaced by a tyrosine (Y). 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

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.4

DANN

Benign

0.71

DEOGEN2

Benign

0.015

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.47

M_CAP

Benign

0.0021

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.1

REVEL

Benign

0.092

Sift

Benign

0.030

Sift4G

Uncertain

0.013

Polyphen

0.45

Vest4

0.23

MVP

0.030

MPC

0.10

ClinPred

0.068

GERP RS

-8.9

Varity_R

0.054

gMVP

0.39

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