1-155284025-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_020897.3(HCN3):c.760C>A(p.Leu254Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,614,038 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 (★).
Frequency
Consequence
NM_020897.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HCN3 | ENST00000368358.4 | c.760C>A | p.Leu254Ile | missense_variant | Exon 3 of 8 | 1 | NM_020897.3 | ENSP00000357342.3 | ||
HCN3 | ENST00000496230.5 | n.652C>A | non_coding_transcript_exon_variant | Exon 3 of 8 | 2 | |||||
HCN3 | ENST00000467204.1 | n.304-514C>A | intron_variant | Intron 1 of 4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251474Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135912
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461858Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727242
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74344
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.760C>A (p.L254I) alteration is located in exon 3 (coding exon 3) of the HCN3 gene. This alteration results from a C to A substitution at nucleotide position 760, causing the leucine (L) at amino acid position 254 to be replaced by an isoleucine (I). 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