rs1032793565
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4
The NM_004387.4(NKX2-5):c.206T>G(p.Leu69Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. L69P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_004387.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NKX2-5 | NM_004387.4 | c.206T>G | p.Leu69Arg | missense_variant | 1/2 | ENST00000329198.5 | |
NKX2-5 | NM_001166176.2 | c.206T>G | p.Leu69Arg | missense_variant | 1/2 | ||
NKX2-5 | NM_001166175.2 | c.206T>G | p.Leu69Arg | missense_variant | 1/2 | ||
NKX2-5 | XM_017009071.3 | c.206T>G | p.Leu69Arg | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKX2-5 | ENST00000329198.5 | c.206T>G | p.Leu69Arg | missense_variant | 1/2 | 1 | NM_004387.4 | P1 | |
NKX2-5 | ENST00000424406.2 | c.206T>G | p.Leu69Arg | missense_variant | 1/2 | 1 | |||
NKX2-5 | ENST00000521848.1 | c.206T>G | p.Leu69Arg | missense_variant | 1/2 | 2 | |||
NKX2-5 | ENST00000517440.1 | c.206T>G | p.Leu69Arg | missense_variant | 1/2 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Atrial septal defect 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2017 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NKX2-5-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 69 of the NKX2-5 protein (p.Leu69Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at