4-62070214-A-G

Variant summary

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

The NM_001387552.1(ADGRL3):​c.3938A>G​(p.Asn1313Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ADGRL3
NM_001387552.1 missense

Scores

5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1679107).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADGRL3NM_001387552.1 linkc.3938A>G p.Asn1313Ser 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.3938A>G p.Asn1313Ser missense_variant Exon 27 of 27 NM_001387552.1 ENSP00000507980.1 A0A804HKL8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249138
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135174
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461772
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3716A>G (p.N1239S) alteration is located in exon 23 (coding exon 23) of the ADGRL3 gene. This alteration results from a A to G substitution at nucleotide position 3716, causing the asparagine (N) at amino acid position 1239 to be replaced by a serine (S). 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
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0068
.;T;T;T;T;T
Eigen
Benign
0.043
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.17
T;T;T;T;T;T
MetaSVM
Benign
-0.90
T
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.63
N;N;N;N;N;N
REVEL
Benign
0.24
Sift
Benign
0.20
T;T;T;T;T;T
Sift4G
Benign
0.20
T;T;T;T;T;T
Vest4
0.16
MutPred
0.60
Gain of disorder (P = 0.0619);.;.;.;.;.;
MVP
0.20
MPC
0.39
ClinPred
0.68
D
GERP RS
5.1
gMVP
0.46

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: rs1403281265; hg19: chr4-62935932; API