Variant 3-100633265-C-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.335C>T(p.Ala112Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000881 in 1,416,672 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00091 ( 0 hom. )

Consequence

ADGRG7
NM_032787.3 missense, splice_region

Scores

Splicing: ADA: 0.05710

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.138

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:

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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=0.027935266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG7	NM_032787.3 linkuse as main transcript	c.335C>T	p.Ala112Val	missense_variant, splice_region_variant	4/16	ENST00000273352.8	NP_116176.2
ADGRG7	XM_047449088.1 linkuse as main transcript	c.43-2412C>T		intron_variant			XP_047305044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG7	ENST00000273352.8 linkuse as main transcript	c.335C>T	p.Ala112Val	missense_variant, splice_region_variant	4/16	1	NM_032787.3	ENSP00000273352	P1

Frequencies

GnomAD3 genomes

AF:

0.000639

AC:

AN:

151848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.00125

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.000627

AC:

108

AN:

172174

Hom.:

AF XY:

0.000648

AC XY:

AN XY:

95732

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000640

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000515

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.000285

GnomAD4 exome

AF:

0.000910

AC:

1151

AN:

1264824

Hom.:

Cov.:

AF XY:

0.000891

AC XY:

555

AN XY:

622614

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000407

Gnomad4 ASJ exome

AF:

0.0000487

Gnomad4 EAS exome

AF:

0.0000306

Gnomad4 SAS exome

AF:

0.0000620

Gnomad4 FIN exome

AF:

0.0000434

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.000411

GnomAD4 genome

AF:

0.000639

AC:

AN:

151848

Hom.:

Cov.:

AF XY:

0.000607

AC XY:

AN XY:

74138

show subpopulations

Gnomad4 AFR

AF:

0.000218

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.000960

Alfa

AF:

0.000863

Hom.:

Bravo

AF:

0.000514

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000568

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

Jul 21, 2022

The c.335C>T (p.A112V) alteration is located in exon 4 (coding exon 4) of the ADGRG7 gene. This alteration results from a C to T substitution at nucleotide position 335, causing the alanine (A) at amino acid position 112 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

0.13

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.53

M_CAP

Benign

0.0044

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.87

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.8

REVEL

Benign

0.033

Sift

Uncertain

0.027

Sift4G

Benign

0.21

Polyphen

0.24

Vest4

0.13

MVP

0.22

MPC

0.063

ClinPred

0.048

GERP RS

2.9

Varity_R

0.060

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.057

dbscSNV1_RF

Benign

0.19

SpliceAI score (max)

0.15

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