4-61892773-G-T

Variant names:

• chr4-61892773-G-T
• rs35106420
• NM_001387552.1:c.1598G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001387552.1(ADGRL3):​c.1598G>T​(p.Arg533Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ADGRL3 NM_001387552.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387552.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	NM_001387552.1	MANE Select	c.1598G>T	p.Arg533Leu	missense	Exon 10 of 27	NP_001374481.1
	ADGRL3	NM_001322402.3		c.1598G>T	p.Arg533Leu	missense	Exon 10 of 26	NP_001309331.1
	ADGRL3	NM_001371344.2		c.1598G>T	p.Arg533Leu	missense	Exon 9 of 24	NP_001358273.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	ENST00000683033.1	MANE Select	c.1598G>T	p.Arg533Leu	missense	Exon 10 of 27	ENSP00000507980.1
	ADGRL3	ENST00000512091.6	TSL:1	c.1394G>T	p.Arg465Leu	missense	Exon 9 of 26	ENSP00000423388.1
	ADGRL3	ENST00000506720.5	TSL:5	c.1598G>T	p.Arg533Leu	missense	Exon 8 of 25	ENSP00000420931.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461660 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111834

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.028
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.84	T
PhyloP100		4.8
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.17
Sift	Benign	0.19	T
Sift4G	Benign	0.32	T
Polyphen		0.74	P
Vest4		0.77
MutPred		0.26		Loss of MoRF binding (P = 0.0332)
MVP		0.17
MPC		0.39
ClinPred		0.52	D
GERP RS		5.0
gMVP		0.51
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs35106420; hg19: chr4-62758491;