19-14151030-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_014921.5(ADGRL1):c.4253A>T(p.Tyr1418Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000016 in 1,497,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000081 ( 0 hom., cov: 28)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
ADGRL1
NM_014921.5 missense
NM_014921.5 missense
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: 5.74
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, ADGRL1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.29660812).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRL1 | NM_014921.5 | c.4253A>T | p.Tyr1418Phe | missense_variant | 23/23 | ENST00000361434.8 | |
ADGRL1-AS1 | NR_045214.1 | n.73-4122T>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRL1 | ENST00000361434.8 | c.4253A>T | p.Tyr1418Phe | missense_variant | 23/23 | 1 | NM_014921.5 | A1 | |
ADGRL1-AS1 | ENST00000588387.2 | n.79-4122T>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000806 AC: 1AN: 124016Hom.: 0 Cov.: 28
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GnomAD4 exome AF: 0.0000167 AC: 23AN: 1373148Hom.: 0 Cov.: 37 AF XY: 0.0000208 AC XY: 14AN XY: 674122
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GnomAD4 genome ? AF: 0.00000806 AC: 1AN: 124016Hom.: 0 Cov.: 28 AF XY: 0.0000171 AC XY: 1AN XY: 58546
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | The c.4268A>T (p.Y1423F) alteration is located in exon 24 (coding exon 23) of the ADGRL1 gene. This alteration results from a A to T substitution at nucleotide position 4268, causing the tyrosine (Y) at amino acid position 1423 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
D;D
Sift4G
Uncertain
D;D
Polyphen
D;P
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at