NM_145805.3:c.521C>T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_145805.3(ISL2):c.521C>T(p.Ser174Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,602,526 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
Consequence
NM_145805.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ISL2 | ENST00000290759.9 | c.521C>T | p.Ser174Leu | missense_variant | Exon 4 of 6 | 1 | NM_145805.3 | ENSP00000290759.4 | ||
ISL2 | ENST00000558656.1 | n.258C>T | non_coding_transcript_exon_variant | Exon 3 of 5 | 5 | ENSP00000453837.1 | ||||
ENSG00000259514 | ENST00000559539.1 | n.380G>A | non_coding_transcript_exon_variant | Exon 2 of 3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152124Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000424 AC: 1AN: 235654Hom.: 0 AF XY: 0.00000774 AC XY: 1AN XY: 129218
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1450402Hom.: 0 Cov.: 41 AF XY: 0.00000277 AC XY: 2AN XY: 720966
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152124Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74340
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.521C>T (p.S174L) alteration is located in exon 4 (coding exon 4) of the ISL2 gene. This alteration results from a C to T substitution at nucleotide position 521, causing the serine (S) at amino acid position 174 to be replaced by a leucine (L). 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