12-130992364-C-T

Variant summary

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

The NM_198827.5(ADGRD1):​c.938C>T​(p.Ser313Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

ADGRD1
NM_198827.5 missense

Scores

7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15
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]
ADGRD1-AS1 (HGNC:53314): (ADGRD1 antisense RNA 1)

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=0.2092003).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADGRD1NM_198827.5 linkuse as main transcriptc.938C>T p.Ser313Leu missense_variant 8/25 ENST00000261654.10
ADGRD1-AS1NR_131951.1 linkuse as main transcriptn.70-1227G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADGRD1ENST00000261654.10 linkuse as main transcriptc.938C>T p.Ser313Leu missense_variant 8/251 NM_198827.5 P4Q6QNK2-1
ADGRD1ENST00000535015.5 linkuse as main transcriptc.1034C>T p.Ser345Leu missense_variant 9/261 A1Q6QNK2-4
ADGRD1-AS1ENST00000542980.1 linkuse as main transcriptn.262G>A non_coding_transcript_exon_variant 2/34
ADGRD1-AS1ENST00000536673.1 linkuse as main transcriptn.61-1227G>A intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152154
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251238
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135778
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461520
Hom.:
0
Cov.:
30
AF XY:
0.00000825
AC XY:
6
AN XY:
727084
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000766
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152154
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

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 GeneticsMay 17, 2023The c.938C>T (p.S313L) alteration is located in exon 8 (coding exon 8) of the ADGRD1 gene. This alteration results from a C to T substitution at nucleotide position 938, causing the serine (S) at amino acid position 313 to be replaced by a leucine (L). 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
0.13
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
0.0
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.065
T;.
Eigen
Benign
0.081
Eigen_PC
Benign
0.016
FATHMM_MKL
Benign
0.65
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-0.82
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-2.8
D;N
REVEL
Benign
0.21
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
0.97
D;.
Vest4
0.17
MutPred
0.43
Loss of disorder (P = 0.0238);.;
MVP
0.57
MPC
0.46
ClinPred
0.97
D
GERP RS
5.5
Varity_R
0.34
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs764392187; hg19: chr12-131476909; COSMIC: COSV55443294; COSMIC: COSV55443294; API