12-54011092-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_022658.4(HOXC8):c.440C>T(p.Pro147Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,612,900 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_022658.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HOXC8 | ENST00000040584.6 | c.440C>T | p.Pro147Leu | missense_variant | Exon 2 of 2 | 1 | NM_022658.4 | ENSP00000040584.4 | ||
ENSG00000273049 | ENST00000513209.1 | c.167-23186C>T | intron_variant | Intron 1 of 1 | 3 | ENSP00000476742.1 | ||||
HOXC6 | ENST00000509328.1 | c.-73+16076C>T | intron_variant | Intron 1 of 2 | 3 | ENSP00000423898.1 | ||||
HOXC6 | ENST00000504315.1 | c.-192-17484C>T | intron_variant | Intron 1 of 1 | 3 | ENSP00000424124.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152056Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000187 AC: 47AN: 251194Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135782
GnomAD4 exome AF: 0.0000500 AC: 73AN: 1460844Hom.: 1 Cov.: 31 AF XY: 0.0000578 AC XY: 42AN XY: 726842
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152056Hom.: 0 Cov.: 30 AF XY: 0.0000404 AC XY: 3AN XY: 74256
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.440C>T (p.P147L) alteration is located in exon 2 (coding exon 2) of the HOXC8 gene. This alteration results from a C to T substitution at nucleotide position 440, causing the proline (P) at amino acid position 147 to be replaced by a leucine (L). 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