12-130971571-G-A

Position:

• chr12-130971571-G-A

Variant summary

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

The NM_198827.5(ADGRD1):​c.301G>A​(p.Gly101Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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: ADGRD1 NM_198827.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.38

Genes affected

ADGRD1 (HGNC:19893): (adhesion G protein-coupled receptor D1) The adhesion G-protein-coupled receptors (GPCRs), including GPR133, are membrane-bound proteins with long N termini containing multiple domains. GPCRs, or GPRs, contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins (summary by Bjarnadottir et al., 2004 [PubMed 15203201]).[supplied by OMIM, Nov 2010]

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=0.3152333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRD1	NM_198827.5	c.301G>A	p.Gly101Ser	missense_variant	4/25	ENST00000261654.10	NP_942122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRD1	ENST00000261654.10	c.301G>A	p.Gly101Ser	missense_variant	4/25	1	NM_198827.5	ENSP00000261654.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Nov 09, 2024

The c.301G>A (p.G101S) alteration is located in exon 4 (coding exon 4) of the ADGRD1 gene. This alteration results from a G to A substitution at nucleotide position 301, causing the glycine (G) at amino acid position 101 to be replaced by a serine (S). 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	0.082
BayesDel_addAF	Benign	0.0011	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T;T;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.44	T
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.094	T;T;T
Sift4G	Benign	0.070	T;T;T
Polyphen		0.62	P;.;.
Vest4		0.33
MutPred		0.42		Loss of catalytic residue at G101 (P = 0.004);Loss of catalytic residue at G101 (P = 0.004);.;
MVP		0.78
MPC		0.34
ClinPred		0.92	D
GERP RS		4.7
Varity_R		0.11
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs972270917; hg19: chr12-131456116;