chr5-45262028-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_021072.4(HCN1):c.2566G>A(p.Val856Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. V856L) has been classified as Uncertain significance.
Frequency
Consequence
NM_021072.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN1 | NM_021072.4 | c.2566G>A | p.Val856Ile | missense_variant | 8/8 | ENST00000303230.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN1 | ENST00000303230.6 | c.2566G>A | p.Val856Ile | missense_variant | 8/8 | 1 | NM_021072.4 | P2 | |
HCN1 | ENST00000673735.1 | c.*791G>A | 3_prime_UTR_variant | 9/9 | A2 | ||||
HCN1 | ENST00000637305.1 | n.1729G>A | non_coding_transcript_exon_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250812Hom.: 1 AF XY: 0.0000147 AC XY: 2AN XY: 135754
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 4AN: 1461798Hom.: 1 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727204
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 21, 2023 | The c.2566G>A (p.V856I) alteration is located in exon 8 (coding exon 8) of the HCN1 gene. This alteration results from a G to A substitution at nucleotide position 2566, causing the valine (V) at amino acid position 856 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