12-6774858-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002286.6(LAG3):c.775G>A(p.Val259Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,611,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002286.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAG3 | NM_002286.6 | c.775G>A | p.Val259Ile | missense_variant | 4/8 | ENST00000203629.3 | |
LAG3 | NM_001414176.1 | c.775G>A | p.Val259Ile | missense_variant | 4/8 | ||
LAG3 | NM_001414177.1 | c.775G>A | p.Val259Ile | missense_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAG3 | ENST00000203629.3 | c.775G>A | p.Val259Ile | missense_variant | 4/8 | 1 | NM_002286.6 | P2 | |
LAG3 | ENST00000441671.6 | c.775G>A | p.Val259Ile | missense_variant | 4/5 | 1 | A2 | ||
LAG3 | ENST00000538079.1 | n.1397G>A | non_coding_transcript_exon_variant | 3/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250076Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135132
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459204Hom.: 0 Cov.: 33 AF XY: 0.00000689 AC XY: 5AN XY: 725406
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74282
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2021 | The c.775G>A (p.V259I) alteration is located in exon 4 (coding exon 4) of the LAG3 gene. This alteration results from a G to A substitution at nucleotide position 775, causing the valine (V) at amino acid position 259 to be replaced by an isoleucine (I). 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