Genetic Variant ADGRL1:p.Pro1393Gln (chr19-14151105-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014921.5(ADGRL1):c.4178C>A(p.Pro1393Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P1393L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ADGRL1
NM_014921.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.29

Publications

0 publications found

Variant links:

Genes affected

ADGRL1 (HGNC:20973): (adhesion G protein-coupled receptor L1) 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. Latrophilin-1 has been shown to recruit the neurotoxin from black widow spider venom, alpha-latrotoxin, to the synapse plasma membrane. Alternative splicing results in multiple variants encoding distinct isoforms.[provided by RefSeq, Oct 2008]

ADGRL1 links:

ADGRL1-AS1 (HGNC:55309): (ADGRL1 antisense RNA 1)

ADGRL1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20620054).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014921.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRL1	NM_014921.5	MANE Select	c.4178C>A	p.Pro1393Gln	missense	Exon 23 of 23	NP_055736.2
ADGRL1	NM_001008701.3		c.4193C>A	p.Pro1398Gln	missense	Exon 24 of 24	NP_001008701.1	O94910-1
ADGRL1-AS1	NR_045214.1		n.73-4047G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRL1	ENST00000361434.8	TSL:1 MANE Select	c.4178C>A	p.Pro1393Gln	missense	Exon 23 of 23	ENSP00000355328.2	O94910-2
ADGRL1	ENST00000340736.10	TSL:1	c.4193C>A	p.Pro1398Gln	missense	Exon 24 of 24	ENSP00000340688.5	O94910-1
ADGRL1-AS1	ENST00000588387.3	TSL:1	n.80-4047G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000646

AC:

AN:

154812

AF XY:

0.0000119

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

7.16e-7

AC:

AN:

1397362

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32076

American (AMR)

AF:

0.00

AC:

AN:

37290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23230

East Asian (EAS)

AF:

0.00

AC:

AN:

37116

South Asian (SAS)

AF:

0.00

AC:

AN:

76238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4012

European-Non Finnish (NFE)

AF:

9.24e-7

AC:

AN:

1082096

Other (OTH)

AF:

0.00

AC:

AN:

57704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.44

PhyloP100

7.3

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.6

REVEL

Benign

0.27

Sift

Benign

0.18

Sift4G

Benign

0.12

Polyphen

0.85

Vest4

0.19

MutPred

0.40

Loss of glycosylation at P1398 (P = 0.0387)

MVP

0.043

MPC

1.1

ClinPred

0.92

GERP RS

2.9

Varity_R

0.17

gMVP

0.53

Mutation Taster

=65/35

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over