4-62070654-G-T

Variant summary

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

The NM_001387552.1(ADGRL3):​c.4378G>T​(p.Ala1460Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ADGRL3
NM_001387552.1 missense

Scores

3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.40
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]

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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=0.14504999).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADGRL3NM_001387552.1 linkc.4378G>T p.Ala1460Ser missense_variant Exon 27 of 27 ENST00000683033.1 NP_001374481.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADGRL3ENST00000683033.1 linkc.4378G>T p.Ala1460Ser missense_variant Exon 27 of 27 NM_001387552.1 ENSP00000507980.1 A0A804HKL8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1399302
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
690160
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:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
22
DANN
Benign
0.86
DEOGEN2
Benign
0.0083
.;T;T;T;T;T
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.92
D;D;D;D;D;D
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.15
T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.17
N;N;N;N;N;N
REVEL
Benign
0.053
Sift
Benign
0.28
T;T;T;T;T;T
Sift4G
Benign
0.57
T;T;T;T;T;T
Vest4
0.032
MutPred
0.31
Gain of glycosylation at A1386 (P = 0.0029);.;.;.;.;.;
MVP
0.15
MPC
0.29
ClinPred
0.63
D
GERP RS
5.4
gMVP
0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-62936372; API