chr12-131005989-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198827.5(ADGRD1):​c.1273G>A​(p.Gly425Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000887 in 1,611,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

ADGRD1
NM_198827.5 missense

Scores

1
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADGRD1NM_198827.5 linkuse as main transcriptc.1273G>A p.Gly425Ser missense_variant 12/25 ENST00000261654.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADGRD1ENST00000261654.10 linkuse as main transcriptc.1273G>A p.Gly425Ser missense_variant 12/251 NM_198827.5 P4Q6QNK2-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152076
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000240
AC:
6
AN:
249876
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135106
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000529
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000932
AC:
136
AN:
1459654
Hom.:
0
Cov.:
32
AF XY:
0.0000895
AC XY:
65
AN XY:
726112
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:
0.000121
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152076
Hom.:
0
Cov.:
34
AF XY:
0.0000269
AC XY:
2
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000124
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 GeneticsJul 13, 2021The c.1273G>A (p.G425S) alteration is located in exon 12 (coding exon 12) of the ADGRD1 gene. This alteration results from a G to A substitution at nucleotide position 1273, causing the glycine (G) at amino acid position 425 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
Uncertain
0.48
BayesDel_addAF
Benign
-0.080
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.034
T;.
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.49
T;T
MetaSVM
Benign
-0.82
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.5
N;N
REVEL
Benign
0.25
Sift
Benign
0.070
T;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.96
P;.
Vest4
0.46
MVP
0.66
MPC
0.69
ClinPred
0.70
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.19
gMVP
0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs374575404; hg19: chr12-131490534; API