rs734644

Positions:

• chr4-61935010-T-A
• chr4-61935010-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001387552.1(ADGRL3):​c.2283T>A​(p.Asn761Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 11/18 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRL3 NM_001387552.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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]

ADGRL3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.2283T>A	p.Asn761Lys	missense_variant	14/27	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.2283T>A	p.Asn761Lys	missense_variant	14/27		NM_001387552.1	ENSP00000507980.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461318 Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0 AN XY: 726930

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: 0.00

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	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Benign	0.85
DEOGEN2	Benign	0.0030	.;.;.;T;T;T;.;T;.;T;T;T;T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.038
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.94	T
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.75	N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.065
Sift	Benign	0.93	T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.75	T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.59	P;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.66
MutPred		0.45		Gain of ubiquitination at N693 (P = 0.0162);Gain of ubiquitination at N693 (P = 0.0162);.;.;Gain of ubiquitination at N693 (P = 0.0162);.;.;.;Gain of ubiquitination at N693 (P = 0.0162);Gain of ubiquitination at N693 (P = 0.0162);Gain of ubiquitination at N693 (P = 0.0162);.;.;Gain of ubiquitination at N693 (P = 0.0162);
MVP		0.043
MPC		0.45
ClinPred		0.58	D
GERP RS		4.7
gMVP		0.41

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: rs734644; hg19: chr4-62800728;