1-32274419-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005356.5(LCK):c.90G>A(p.Leu30=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000093 in 1,612,734 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 (★). Synonymous variant affecting the same amino acid position (i.e. L30L) has been classified as Likely benign.
Frequency
Consequence
NM_005356.5 synonymous
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 |
---|---|---|---|---|---|---|---|
LCK | NM_005356.5 | c.90G>A | p.Leu30= | synonymous_variant | 2/13 | ENST00000336890.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LCK | ENST00000336890.10 | c.90G>A | p.Leu30= | synonymous_variant | 2/13 | 1 | NM_005356.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250396Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135304
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1460548Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726512
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
Severe combined immunodeficiency due to LCK deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2020 | This variant has not been reported in the literature in individuals with LCK-related disease. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 30 of the LCK mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LCK protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at