rs574618340

Variant names:

• chr4-61892842-C-G
• rs574618340
• NM_001387552.1:c.1667C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-61892842-C-G
• chr4-61892842-C-T

Variant summary

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

The NM_001387552.1(ADGRL3):​c.1667C>G​(p.Ser556Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/20 in silico tools predict a benign 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. S556L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADGRL3 NM_001387552.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	NM_001387552.1	MANE Select	c.1667C>G	p.Ser556Trp	missense	Exon 10 of 27	NP_001374481.1	A0A804HKL8
	ADGRL3	NM_001322402.3		c.1667C>G	p.Ser556Trp	missense	Exon 10 of 26	NP_001309331.1
	ADGRL3	NM_001371344.2		c.1667C>G	p.Ser556Trp	missense	Exon 9 of 24	NP_001358273.1	E7EVD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	ENST00000683033.1	MANE Select	c.1667C>G	p.Ser556Trp	missense	Exon 10 of 27	ENSP00000507980.1	A0A804HKL8
	ADGRL3	ENST00000512091.6	TSL:1	c.1463C>G	p.Ser488Trp	missense	Exon 9 of 26	ENSP00000423388.1	Q9HAR2-2
	ADGRL3	ENST00000506720.5	TSL:5	c.1667C>G	p.Ser556Trp	missense	Exon 8 of 25	ENSP00000420931.1	E7EUW2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	0.091
Eigen_PC	Benign	0.085
FATHMM_MKL	Benign	0.75	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.47	T
PhyloP100		3.0
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.65
MutPred		0.33		Loss of disorder (P = 0.0056)
MVP		0.36
MPC		0.91
ClinPred		0.92	D
GERP RS		5.8
gMVP		0.53
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs574618340; hg19: chr4-62758560; COSMIC: COSV72231044; COSMIC: COSV72231044;