chr3-50608568-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_145071.4(CISH):c.46C>T(p.Arg16Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,550,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. R16Q) has been classified as Likely benign.
Frequency
Consequence
NM_145071.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CISH | NM_145071.4 | c.46C>T | p.Arg16Trp | missense_variant | 2/3 | ENST00000348721.4 | |
CISH | NM_013324.7 | c.97C>T | p.Arg33Trp | missense_variant | 3/4 | ||
CISH | XM_047447398.1 | c.97C>T | p.Arg33Trp | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CISH | ENST00000348721.4 | c.46C>T | p.Arg16Trp | missense_variant | 2/3 | 1 | NM_145071.4 | P1 | |
CISH | ENST00000443053.6 | c.97C>T | p.Arg33Trp | missense_variant | 3/4 | 1 | |||
CISH | ENST00000491847.1 | n.3194C>T | non_coding_transcript_exon_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000436 AC: 8AN: 183476Hom.: 0 AF XY: 0.0000502 AC XY: 5AN XY: 99538
GnomAD4 exome AF: 0.0000200 AC: 28AN: 1398400Hom.: 0 Cov.: 32 AF XY: 0.0000188 AC XY: 13AN XY: 690836
GnomAD4 genome AF: 0.0000459 AC: 7AN: 152352Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74494
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2024 | The c.97C>T (p.R33W) alteration is located in exon 3 (coding exon 2) of the CISH gene. This alteration results from a C to T substitution at nucleotide position 97, causing the arginine (R) at amino acid position 33 to be replaced by a tryptophan (W). 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