chr4-62070666-G-T

Variant names:

• chr4-62070666-G-T
• rs771497064
• NM_001387552.1:c.4390G>T

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.4390G>T​(p.Ala1464Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,551,264 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. 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. A1464T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ADGRL3 NM_001387552.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• 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]

ADGRL3-AS1 (HGNC:50604): (ADGRL3 antisense RNA 1)

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=0.034351498).

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.4390G>T	p.Ala1464Ser	missense	Exon 27 of 27	NP_001374481.1	A0A804HKL8
	ADGRL3	NM_001322402.3		c.4372G>T	p.Ala1458Ser	missense	Exon 26 of 26	NP_001309331.1
	ADGRL3	NM_001371344.2		c.4345G>T	p.Ala1449Ser	missense	Exon 24 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.4390G>T	p.Ala1464Ser	missense	Exon 27 of 27	ENSP00000507980.1	A0A804HKL8
	ADGRL3	ENST00000512091.6	TSL:1	c.*497G>T		3_prime_UTR	Exon 26 of 26	ENSP00000423388.1	Q9HAR2-2
	ADGRL3	ENST00000506720.5	TSL:5	c.4501G>T	p.Ala1501Ser	missense	Exon 25 of 25	ENSP00000420931.1	E7EUW2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151952 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399312 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690156

African (AFR) AF: 0.0000316 AC: 1 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078960

Other (OTH) AF: 0.00 AC: 0 AN: 58008

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151952 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74226

African (AFR) AF: 0.0000484 AC: 2 AN: 41346

American (AMR) AF: 0.0000655 AC: 1 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.028
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.044
Sift	Benign	0.44	T
Sift4G	Benign	0.49	T
Vest4		0.041
MutPred		0.28		Gain of glycosylation at A1390 (P = 0.0019)
MVP		0.16
MPC		0.29
ClinPred		0.094	T
GERP RS		3.3
gMVP		0.21
Mutation Taster		=86/14	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: rs771497064; hg19: chr4-62936384;