chr8-23681225-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_006167.4(NKX3-1):āc.701G>Cā(p.Trp234Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000709 in 1,410,842 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W234R) has been classified as Uncertain significance.
Frequency
Consequence
NM_006167.4 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 |
---|---|---|---|---|---|---|---|
NKX3-1 | NM_006167.4 | c.701G>C | p.Trp234Ser | missense_variant | 2/2 | ENST00000380871.5 | |
LOC107986930 | XR_001745842.2 | n.1312+12475C>G | intron_variant, non_coding_transcript_variant | ||||
NKX3-1 | NM_001256339.1 | c.476G>C | p.Trp159Ser | missense_variant | 3/3 | ||
NKX3-1 | NR_046072.2 | n.36-83G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKX3-1 | ENST00000380871.5 | c.701G>C | p.Trp234Ser | missense_variant | 2/2 | 1 | NM_006167.4 | P2 | |
NKX3-1 | ENST00000523261.1 | c.476G>C | p.Trp159Ser | missense_variant | 3/3 | 1 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000886 AC: 2AN: 225616Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 121920
GnomAD4 exome AF: 0.00000709 AC: 10AN: 1410842Hom.: 0 Cov.: 31 AF XY: 0.00000576 AC XY: 4AN XY: 694792
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2021 | The c.701G>C (p.W234S) alteration is located in exon 2 (coding exon 2) of the NKX3-1 gene. This alteration results from a G to C substitution at nucleotide position 701, causing the tryptophan (W) at amino acid position 234 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at