NM_001189.4:c.700C>T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001189.4(NKX3-2):c.700C>T(p.Pro234Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000933 in 1,607,244 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 (★).
Frequency
Consequence
NM_001189.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NKX3-2 | NM_001189.4 | c.700C>T | p.Pro234Ser | missense_variant | Exon 2 of 2 | ENST00000382438.6 | NP_001180.1 | |
NKX3-2 | XM_047416049.1 | c.700C>T | p.Pro234Ser | missense_variant | Exon 3 of 3 | XP_047272005.1 | ||
NKX3-2 | XM_047416050.1 | c.700C>T | p.Pro234Ser | missense_variant | Exon 3 of 3 | XP_047272006.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000342 AC: 8AN: 233836Hom.: 0 AF XY: 0.0000312 AC XY: 4AN XY: 128338
GnomAD4 exome AF: 0.00000893 AC: 13AN: 1455056Hom.: 0 Cov.: 31 AF XY: 0.0000111 AC XY: 8AN XY: 723470
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74338
ClinVar
Submissions by phenotype
NKX3-2-related disorder Uncertain:1
The NKX3-2 c.700C>T variant is predicted to result in the amino acid substitution p.Pro234Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-13543919-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
not provided Uncertain:1
This variant is present in population databases (rs746738857, gnomAD 0.02%). 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 1439291). This variant has not been reported in the literature in individuals affected with NKX3-2-related conditions. This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 234 of the NKX3-2 protein (p.Pro234Ser). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at