12-130954504-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198827.5(ADGRD1):ā€‹c.39G>Cā€‹(p.Trp13Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,320 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

ADGRD1
NM_198827.5 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25784296).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADGRD1NM_198827.5 linkuse as main transcriptc.39G>C p.Trp13Cys missense_variant 1/25 ENST00000261654.10 NP_942122.2 Q6QNK2-1Q9NSM3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADGRD1ENST00000261654.10 linkuse as main transcriptc.39G>C p.Trp13Cys missense_variant 1/251 NM_198827.5 ENSP00000261654.5 Q6QNK2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.93e-7
AC:
1
AN:
1443320
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
716016
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:
9.08e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 19, 2024The c.39G>C (p.W13C) alteration is located in exon 1 (coding exon 1) of the ADGRD1 gene. This alteration results from a G to C substitution at nucleotide position 39, causing the tryptophan (W) at amino acid position 13 to be replaced by a cysteine (C). 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
0.15
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
21
DANN
Benign
0.85
DEOGEN2
Benign
0.054
T;T;.
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.69
T;T;T
M_CAP
Benign
0.075
D
MetaRNN
Benign
0.26
T;T;T
MetaSVM
Benign
-0.82
T
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.99
N;N;N
REVEL
Benign
0.20
Sift
Benign
0.063
T;D;T
Sift4G
Uncertain
0.027
D;T;D
Polyphen
0.98
D;.;.
Vest4
0.17
MutPred
0.61
Loss of MoRF binding (P = 0.053);Loss of MoRF binding (P = 0.053);Loss of MoRF binding (P = 0.053);
MVP
0.21
MPC
0.26
ClinPred
0.22
T
GERP RS
1.5
Varity_R
0.18
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr12-131439049; API