chr5-173232621-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004387.4(NKX2-5):c.923T>C(p.Ile308Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,461,176 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I308V) has been classified as Uncertain significance.
Frequency
Consequence
NM_004387.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NKX2-5 | NM_004387.4 | c.923T>C | p.Ile308Thr | missense_variant | 2/2 | ENST00000329198.5 | |
NKX2-5 | NM_001166175.2 | c.*876T>C | 3_prime_UTR_variant | 2/2 | |||
NKX2-5 | NM_001166176.2 | c.*722T>C | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKX2-5 | ENST00000329198.5 | c.923T>C | p.Ile308Thr | missense_variant | 2/2 | 1 | NM_004387.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250204Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135584
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1461176Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9AN XY: 726934
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Atrial septal defect 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NKX2-5 protein function. This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. This variant is present in population databases (rs771088497, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 308 of the NKX2-5 protein (p.Ile308Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at