rs148616574

Variant names:

• chr4-61733233-C-A
• rs148616574
• NM_001387552.1:c.1078C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-61733233-C-A
• chr4-61733233-C-G
• chr4-61733233-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001387552.1(ADGRL3):​c.1078C>A​(p.Pro360Thr) 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. 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. P360A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRL3 NM_001387552.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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]

ACMG classification

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, 0.878

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.1078C>A	p.Pro360Thr	missense_variant	Exon 8 of 27	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.1078C>A	p.Pro360Thr	missense_variant	Exon 8 of 27		NM_001387552.1	ENSP00000507980.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	.;.;.;D;D;D;.;D;.;D;D;D;D;D
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	1.0	D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Pathogenic	0.51	D
MetaRNN	Pathogenic	0.88	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.83	D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-6.2	D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.95
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;.;.;.;.;.;D;.;.;.;.;.;.;.
Vest4		0.78
MutPred		0.69		Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);.;.;Gain of relative solvent accessibility (P = 0.1684);.;.;.;Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);.;.;Gain of relative solvent accessibility (P = 0.1684);
MVP		0.84
MPC		1.1
ClinPred		1.0	D
GERP RS		5.3
gMVP		0.84

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

Other links and lift over

dbSNP: rs148616574; hg19: chr4-62598951;