chr19-35904615-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003332.4(TYROBP):c.296C>G(p.Ser99Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,128 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S99L) has been classified as Uncertain significance.
Frequency
Consequence
NM_003332.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYROBP | NM_003332.4 | c.296C>G | p.Ser99Trp | missense_variant | 5/5 | ENST00000262629.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYROBP | ENST00000262629.9 | c.296C>G | p.Ser99Trp | missense_variant | 5/5 | 1 | NM_003332.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 151954Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249802Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 134966
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461174Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726746
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 151954Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74226
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 13, 2023 | The c.296C>G (p.S99W) alteration is located in exon 5 (coding exon 5) of the TYROBP gene. This alteration results from a C to G substitution at nucleotide position 296, causing the serine (S) at amino acid position 99 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