17-48728454-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006361.6(HOXB13):āc.140A>Gā(p.Asn47Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,613,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N47K) has been classified as Uncertain significance.
Frequency
Consequence
NM_006361.6 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 |
---|---|---|---|---|---|---|---|
HOXB13 | NM_006361.6 | c.140A>G | p.Asn47Ser | missense_variant | 1/2 | ENST00000290295.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOXB13 | ENST00000290295.8 | c.140A>G | p.Asn47Ser | missense_variant | 1/2 | 1 | NM_006361.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 249214Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135108
GnomAD4 exome AF: 0.000111 AC: 162AN: 1460954Hom.: 0 Cov.: 33 AF XY: 0.000111 AC XY: 81AN XY: 726760
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 23, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with a personal history of prostate cancer in published literature (Akbari 2012); This variant is associated with the following publications: (PMID: 22781434, 28272408) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 47 of the HOXB13 protein (p.Asn47Ser). This variant is present in population databases (rs748333323, gnomAD 0.006%). This missense change has been observed in individual(s) with prostate cancer (PMID: 22781434). ClinVar contains an entry for this variant (Variation ID: 483487). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Prostate cancer, hereditary, 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
HOXB13-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 01, 2023 | The HOXB13 c.140A>G variant is predicted to result in the amino acid substitution p.Asn47Ser. This variant was reported in an individual with prostate cancer (Akbari et al. 2012. PubMed ID: 22781434). This variant is reported in 0.0063% of alleles in individuals of European (Non-Finnish) descent in gnomAD and is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/483487/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 26, 2023 | The p.N47S variant (also known as c.140A>G), located in coding exon 1 of the HOXB13 gene, results from an A to G substitution at nucleotide position 140. The asparagine at codon 47 is replaced by serine, an amino acid with highly similar properties. This alteration was detected in 1/1843 individuals with prostate cancer and was not detected in 2225 controls (Akbari MR et al. J. Natl. Cancer Inst., 2012 Aug;104:1260-2). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at