rs766951668

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001387552.1(ADGRL3):​c.530C>G​(p.Pro177Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 11/18 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P177L) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Failed GnomAD Quality Control

Consequence

ADGRL3
NM_001387552.1 missense

Scores

12
2
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
ADGRL3 (HGNC:20974): (adhesion G protein-coupled receptor L3) This gene encodes a member of the latrophilin subfamily of G-protein coupled receptors (GPCR). Latrophilins may function in both cell adhesion and signal transduction. In experiments with non-human species, endogenous proteolytic cleavage within a cysteine-rich GPS (G-protein-coupled-receptor proteolysis site) domain resulted in two subunits (a large extracellular N-terminal cell adhesion subunit and a subunit with substantial similarity to the secretin/calcitonin family of GPCRs) being non-covalently bound at the cell membrane. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADGRL3NM_001387552.1 linkc.530C>G p.Pro177Arg missense_variant Exon 6 of 27 ENST00000683033.1 NP_001374481.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADGRL3ENST00000683033.1 linkc.530C>G p.Pro177Arg missense_variant Exon 6 of 27 NM_001387552.1 ENSP00000507980.1 A0A804HKL8

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
151842
Hom.:
0
Cov.:
32
FAILED QC
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000659
AC:
1
AN:
151842
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74150
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:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.079
.;.;.;T;T;T;.;T;.;T;T;T;T;T
Eigen
Pathogenic
0.96
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
1.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
0.29
D
MetaRNN
Pathogenic
0.89
D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.33
T
PrimateAI
Pathogenic
0.89
D
PROVEAN
Pathogenic
-7.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
0.65
Sift
Uncertain
0.028
D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;.;.;.;.;.;D;.;.;.;.;.;.;.
Vest4
0.93
MutPred
0.66
Gain of solvent accessibility (P = 0.0808);Gain of solvent accessibility (P = 0.0808);.;.;Gain of solvent accessibility (P = 0.0808);.;.;.;Gain of solvent accessibility (P = 0.0808);Gain of solvent accessibility (P = 0.0808);Gain of solvent accessibility (P = 0.0808);.;.;Gain of solvent accessibility (P = 0.0808);
MVP
0.46
MPC
1.0
ClinPred
1.0
D
GERP RS
5.5
gMVP
0.98

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: rs766951668; hg19: chr4-62542600; API