rs149255851
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_138713.4(NFAT5):c.2678C>A(p.Thr893Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000737 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 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. T893M) has been classified as Uncertain significance.
Frequency
Consequence
NM_138713.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFAT5 | NM_138713.4 | c.2678C>A | p.Thr893Lys | missense_variant | 13/15 | ENST00000349945.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFAT5 | ENST00000349945.7 | c.2678C>A | p.Thr893Lys | missense_variant | 13/15 | 1 | NM_138713.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250716Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135620
GnomAD4 exome AF: 0.0000780 AC: 114AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.0000688 AC XY: 50AN XY: 727234
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74332
ClinVar
Submissions by phenotype
Immunodeficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2023 | This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 799 of the NFAT5 protein (p.Thr799Lys). This variant is present in population databases (rs149255851, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with NFAT5-related conditions. ClinVar contains an entry for this variant (Variation ID: 577688). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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