rs776938745
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_000081.4(LYST):c.6238G>C(p.Ala2080Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000329 in 1,613,240 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A2080T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000081.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LYST | NM_000081.4 | c.6238G>C | p.Ala2080Pro | missense_variant | 22/53 | ENST00000389793.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LYST | ENST00000389793.7 | c.6238G>C | p.Ala2080Pro | missense_variant | 22/53 | 5 | NM_000081.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250700Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135478
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461096Hom.: 0 Cov.: 30 AF XY: 0.0000303 AC XY: 22AN XY: 726900
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74310
ClinVar
Submissions by phenotype
Chédiak-Higashi syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 05, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2080 of the LYST protein (p.Ala2080Pro). This variant is present in population databases (rs776938745, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with LYST-related conditions. ClinVar contains an entry for this variant (Variation ID: 567810). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 24, 2023 | The c.6238G>C (p.A2080P) alteration is located in exon 22 (coding exon 20) of the LYST gene. This alteration results from a G to C substitution at nucleotide position 6238, causing the alanine (A) at amino acid position 2080 to be replaced by a proline (P). 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