19-35049295-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001384133.1(HPN):c.22C>T(p.Arg8Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000646 in 1,547,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8Q) has been classified as Benign.
Frequency
Consequence
NM_001384133.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HPN | NM_001384133.1 | c.22C>T | p.Arg8Trp | missense_variant | Exon 3 of 13 | ENST00000672452.2 | NP_001371062.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000486 AC: 1AN: 205654Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 109432
GnomAD4 exome AF: 0.00000430 AC: 6AN: 1395276Hom.: 0 Cov.: 32 AF XY: 0.00000438 AC XY: 3AN XY: 685640
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74380
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.22C>T (p.R8W) alteration is located in exon 3 (coding exon 2) of the HPN gene. This alteration results from a C to T substitution at nucleotide position 22, causing the arginine (R) at amino acid position 8 to be replaced by a tryptophan (W). 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