chr4-13542066-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001189.4(NKX3-2):c.929C>A(p.Ser310Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,607,820 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NKX3-2 | NM_001189.4 | c.929C>A | p.Ser310Tyr | missense_variant | Exon 2 of 2 | ENST00000382438.6 | NP_001180.1 | |
NKX3-2 | XM_047416049.1 | c.929C>A | p.Ser310Tyr | missense_variant | Exon 3 of 3 | XP_047272005.1 | ||
NKX3-2 | XM_047416050.1 | c.929C>A | p.Ser310Tyr | missense_variant | Exon 3 of 3 | XP_047272006.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152250Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000717 AC: 17AN: 237048Hom.: 0 AF XY: 0.0000310 AC XY: 4AN XY: 129010
GnomAD4 exome AF: 0.0000117 AC: 17AN: 1455452Hom.: 0 Cov.: 31 AF XY: 0.00000691 AC XY: 5AN XY: 723264
GnomAD4 genome AF: 0.00000656 AC: 1AN: 152368Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74500
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 310 of the NKX3-2 protein (p.Ser310Tyr). This variant is present in population databases (rs771961191, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with NKX3-2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1411460). 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. 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