chr4-61497323-G-A

Variant names:

• chr4-61497323-G-A
• NM_001387552.1:c.30G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387552.1(ADGRL3):​c.30G>A​(p.Met10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 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: 6.9e-7 (0 hom.)
• Consequence: ADGRL3 NM_001387552.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.39
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061766982).

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.30G>A	p.Met10Ile	missense	Exon 3 of 27	NP_001374481.1	A0A804HKL8
	ADGRL3	NM_001322402.3		c.30G>A	p.Met10Ile	missense	Exon 3 of 26	NP_001309331.1
	ADGRL3	NM_001371344.2		c.30G>A	p.Met10Ile	missense	Exon 2 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.30G>A	p.Met10Ile	missense	Exon 3 of 27	ENSP00000507980.1	A0A804HKL8
	ADGRL3	ENST00000512091.6	TSL:1	c.30G>A	p.Met10Ile	missense	Exon 3 of 26	ENSP00000423388.1	Q9HAR2-2
	ADGRL3	ENST00000506720.5	TSL:5	c.30G>A	p.Met10Ile	missense	Exon 1 of 25	ENSP00000420931.1	E7EUW2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454894 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 723804

African (AFR) AF: 0.00 AC: 0 AN: 33002

American (AMR) AF: 0.00 AC: 0 AN: 42942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39446

South Asian (SAS) AF: 0.00 AC: 0 AN: 84860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109552

Other (OTH) AF: 0.00 AC: 0 AN: 60098

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.99	T
PhyloP100		2.4
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.079
Sift	Benign	1.0	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.42		Loss of sheet (P = 0.0315)
MVP		0.12
MPC		0.32
ClinPred		0.11	T
GERP RS		3.1
PromoterAI		-0.045	Neutral
gMVP		0.43
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr4-62363041; COSMIC: COSV72268274;