3-100643399-C-A

Position:

• chr3-100643399-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032787.3(ADGRG7):​c.832C>A​(p.Gln278Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ADGRG7 NM_032787.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.37

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]

ACMG classification

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=0.031417668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG7	NM_032787.3	c.832C>A	p.Gln278Lys	missense_variant	7/16	ENST00000273352.8	NP_116176.2
ADGRG7	XM_047449088.1	c.427C>A	p.Gln143Lys	missense_variant	5/14		XP_047305044.1
ADGRG7	NM_001308362.1	c.62-2546C>A		intron_variant			NP_001295291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG7	ENST00000273352.8	c.832C>A	p.Gln278Lys	missense_variant	7/16	1	NM_032787.3	ENSP00000273352	P1
ADGRG7	ENST00000475887.1	c.62-2546C>A		intron_variant		2		ENSP00000419788
ADGRG7	ENST00000481361.1	n.524C>A		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

May 14, 2024

The c.832C>A (p.Q278K) alteration is located in exon 7 (coding exon 7) of the ADGRG7 gene. This alteration results from a C to A substitution at nucleotide position 832, causing the glutamine (Q) at amino acid position 278 to be replaced by a lysine (K). 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	0.072
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0090
DANN	Benign	0.76
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.012
Sift	Benign	0.90	T
Sift4G	Benign	0.96	T
Polyphen		0.011	B
Vest4		0.091
MutPred		0.32		Loss of ubiquitination at K279 (P = 0.0236);
MVP		0.088
MPC		0.071
ClinPred		0.051	T
GERP RS		-7.2
Varity_R		0.058
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-100362243;