5-51389708-A-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002202.3(ISL1):c.541A>T(p.Thr181Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,613,766 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 (no stars).
Frequency
Consequence
NM_002202.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ISL1 | ENST00000230658.12 | c.541A>T | p.Thr181Ser | missense_variant | Exon 4 of 6 | 1 | NM_002202.3 | ENSP00000230658.7 | ||
ISL1 | ENST00000511384.1 | c.541A>T | p.Thr181Ser | missense_variant | Exon 4 of 6 | 5 | ENSP00000422676.1 | |||
ISL1 | ENST00000505475.3 | n.746A>T | non_coding_transcript_exon_variant | Exon 3 of 5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000270 AC: 41AN: 152096Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000160 AC: 40AN: 250414Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135564
GnomAD4 exome AF: 0.000147 AC: 215AN: 1461554Hom.: 0 Cov.: 33 AF XY: 0.000154 AC XY: 112AN XY: 727092
GnomAD4 genome AF: 0.000269 AC: 41AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74418
ClinVar
Submissions by phenotype
ISL1-related disorder Uncertain:1
The ISL1 c.541A>T variant is predicted to result in the amino acid substitution p.Thr181Ser. To our knowledge, this variant has not been reported in the literature in association with obesity; however, this variant has been previously observed in a genome-wide association study of individuals with isolated classic bladder exstrophy (CBE) (Draaken et al. 2015. PubMed ID: 25763902). This variant is reported in 0.042% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at