12-130992364-C-T
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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
NM_198827.5 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: 2.15
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 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 |
---|---|---|---|---|---|---|---|
ADGRD1 | NM_198827.5 | c.938C>T | p.Ser313Leu | missense_variant | 8/25 | ENST00000261654.10 | |
ADGRD1-AS1 | NR_131951.1 | n.70-1227G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRD1 | ENST00000261654.10 | c.938C>T | p.Ser313Leu | missense_variant | 8/25 | 1 | NM_198827.5 | P4 | |
ADGRD1 | ENST00000535015.5 | c.1034C>T | p.Ser345Leu | missense_variant | 9/26 | 1 | A1 | ||
ADGRD1-AS1 | ENST00000542980.1 | n.262G>A | non_coding_transcript_exon_variant | 2/3 | 4 | ||||
ADGRD1-AS1 | ENST00000536673.1 | n.61-1227G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251238Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135778
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461520Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727084
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74326
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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 | May 17, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of disorder (P = 0.0238);.;
MVP
MPC
ClinPred
D
GERP RS
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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