chr11-70203568-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_003824.4(FADD):c.109G>A(p.Glu37Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,612,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E37E) has been classified as Likely benign.
Frequency
Consequence
NM_003824.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FADD | NM_003824.4 | c.109G>A | p.Glu37Lys | missense_variant | 1/2 | ENST00000301838.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FADD | ENST00000301838.5 | c.109G>A | p.Glu37Lys | missense_variant | 1/2 | 1 | NM_003824.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 245096Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134002
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460226Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 726502
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74370
ClinVar
Submissions by phenotype
FADD-related immunodeficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 16, 2022 | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with FADD-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 37 of the FADD protein (p.Glu37Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at