4-61892956-T-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001387552.1(ADGRL3):c.1781T>C(p.Ile594Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000727 in 1,513,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I594V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001387552.1 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRL3 | NM_001387552.1 | c.1781T>C | p.Ile594Thr | missense_variant, splice_region_variant | 10/27 | ENST00000683033.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRL3 | ENST00000683033.1 | c.1781T>C | p.Ile594Thr | missense_variant, splice_region_variant | 10/27 | NM_001387552.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000259 AC: 4AN: 154480Hom.: 0 AF XY: 0.0000123 AC XY: 1AN XY: 81074
GnomAD4 exome AF: 0.00000661 AC: 9AN: 1361568Hom.: 0 Cov.: 31 AF XY: 0.00000599 AC XY: 4AN XY: 667712
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74338
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2021 | The c.1577T>C (p.I526T) alteration is located in exon 7 (coding exon 7) of the ADGRL3 gene. This alteration results from a T to C substitution at nucleotide position 1577, causing the isoleucine (I) at amino acid position 526 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at