rs200895145

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

4
14
Splicing: ADA: 0.2197
2

Clinical Significance

Not reported in ClinVar

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]

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ACMG classification

Classification made for transcript

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
ADGRG7NM_032787.3 linkc.335C>A p.Ala112Glu missense_variant, splice_region_variant Exon 4 of 16 ENST00000273352.8 NP_116176.2 Q96K78Q6ZMH4
ADGRG7XM_047449088.1 linkc.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
ADGRG7ENST00000273352.8 linkc.335C>A p.Ala112Glu missense_variant, splice_region_variant Exon 4 of 16 1 NM_032787.3 ENSP00000273352.3 Q96K78

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
show subpopulations
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; API