3-100635681-A-G

Position:

• chr3-100635681-A-G

Variant summary

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

The NM_032787.3(ADGRG7):​c.452A>G​(p.Lys151Arg) 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 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K151E) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ADGRG7 NM_032787.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0650

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 (HGNC:):

ACMG classification

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
ADGRG7	NM_032787.3	c.452A>G	p.Lys151Arg	missense_variant	5/16	ENST00000273352.8	NP_116176.2
ADGRG7	XM_047449088.1	c.47A>G	p.Lys16Arg	missense_variant	3/14		XP_047305044.1
ADGRG7	NM_001308362.1	c.-186A>G		5_prime_UTR_variant	1/10		NP_001295291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG7	ENST00000273352.8	c.452A>G	p.Lys151Arg	missense_variant	5/16	1	NM_032787.3	ENSP00000273352.3
ADGRG7	ENST00000475887	c.-186A>G		5_prime_UTR_variant	1/10	2		ENSP00000419788.1
ADGRG7	ENST00000481361.1	n.144A>G		non_coding_transcript_exon_variant	1/4	4
ADGRG7	ENST00000493081.1	n.142A>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32

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.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74342

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

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2024

The c.452A>G (p.K151R) alteration is located in exon 5 (coding exon 5) of the ADGRG7 gene. This alteration results from a A to G substitution at nucleotide position 452, causing the lysine (K) at amino acid position 151 to be replaced by an arginine (R). 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	0.081
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.8
DANN	Benign	0.63
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.0080
Sift	Benign	0.48	T
Sift4G	Benign	0.50	T
Polyphen		0.023	B
Vest4		0.053
MVP		0.055
MPC		0.054
ClinPred		0.055	T
GERP RS		-3.5
Varity_R		0.024
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 39

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1330250809; hg19: chr3-100354525;