12-130981944-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_198827.5(ADGRD1):c.371C>T(p.Ala124Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000861 in 1,613,488 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000091 ( 1 hom. )
Consequence
ADGRD1
NM_198827.5 missense
NM_198827.5 missense
Scores
9
9
Clinical Significance
Conservation
PhyloP100: 6.55
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]
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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 |
---|---|---|---|---|---|---|---|
ADGRD1 | NM_198827.5 | c.371C>T | p.Ala124Val | missense_variant | 5/25 | ENST00000261654.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRD1 | ENST00000261654.10 | c.371C>T | p.Ala124Val | missense_variant | 5/25 | 1 | NM_198827.5 | P4 | |
ADGRD1 | ENST00000535015.5 | c.467C>T | p.Ala156Val | missense_variant | 6/26 | 1 | A1 | ||
ADGRD1 | ENST00000542091.5 | c.311-5151C>T | intron_variant | 3 | |||||
ADGRD1 | ENST00000541143.5 | n.5841C>T | non_coding_transcript_exon_variant | 4/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152162Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251474Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135908
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GnomAD4 exome AF: 0.0000910 AC: 133AN: 1461326Hom.: 1 Cov.: 30 AF XY: 0.0000935 AC XY: 68AN XY: 727024
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152162Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74328
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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 submitter | clinical testing | Ambry Genetics | Aug 09, 2021 | The c.371C>T (p.A124V) alteration is located in exon 5 (coding exon 5) of the ADGRD1 gene. This alteration results from a C to T substitution at nucleotide position 371, causing the alanine (A) at amino acid position 124 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of sheet (P = 0.0104);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at