rs200895145

Variant names:

• chr3-100633265-C-A
• NM_032787.3:c.335C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-100633265-C-A
• chr3-100633265-C-G
• chr3-100633265-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032787.3(ADGRG7):​c.335C>A​(p.Ala112Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000791 in 1,264,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. 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. A112V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: ADGRG7 NM_032787.3 missense, splice_region
• Scores: Splicing: ADA: 0.2197
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27062517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG7	NM_032787.3	c.335C>A	p.Ala112Glu	missense_variant, splice_region_variant	Exon 4 of 16	ENST00000273352.8	NP_116176.2
ADGRG7	XM_047449088.1	c.43-2412C>A		intron_variant	Intron 2 of 13		XP_047305044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG7	ENST00000273352.8	c.335C>A	p.Ala112Glu	missense_variant, splice_region_variant	Exon 4 of 16	1	NM_032787.3	ENSP00000273352.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.91e-7 AC: 1 AN: 1264836 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 622624

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 9.90e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.86	T
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.19
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.015	D
Polyphen		0.99	D
Vest4		0.26
MutPred		0.46		Gain of glycosylation at T109 (P = 0.0126);
MVP		0.45
MPC		0.081
ClinPred		0.92	D
GERP RS		2.9
Varity_R		0.16
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.22
dbscSNV1_RF	Benign	0.28
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.21		Position offset: 0

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: chr3-100352109;