chr1-172659347-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_000639.3(FASLG):c.146C>T(p.Pro49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,609,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. P49P) has been classified as Benign.
Frequency
Consequence
NM_000639.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FASLG | NM_000639.3 | c.146C>T | p.Pro49Leu | missense_variant | 1/4 | ENST00000367721.3 | |
FASLG | NM_001302746.2 | c.146C>T | p.Pro49Leu | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASLG | ENST00000367721.3 | c.146C>T | p.Pro49Leu | missense_variant | 1/4 | 1 | NM_000639.3 | P1 | |
FASLG | ENST00000340030.4 | c.146C>T | p.Pro49Leu | missense_variant | 1/3 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000921 AC: 14AN: 152042Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000123 AC: 3AN: 244580Hom.: 0 AF XY: 0.00000753 AC XY: 1AN XY: 132766
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1457112Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 724918
GnomAD4 genome AF: 0.0000921 AC: 14AN: 152042Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74270
ClinVar
Submissions by phenotype
Autoimmune lymphoproliferative syndrome type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 01, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 49 of the FASLG protein (p.Pro49Leu). This variant is present in population databases (rs370027887, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with FASLG-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at