chr15-73367969-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_005477.3(HCN4):c.302C>T(p.Ala101Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000332 in 1,353,842 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A101A) has been classified as Likely benign.
Frequency
Consequence
NM_005477.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN4 | NM_005477.3 | c.302C>T | p.Ala101Val | missense_variant | 1/8 | ENST00000261917.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN4 | ENST00000261917.4 | c.302C>T | p.Ala101Val | missense_variant | 1/8 | 1 | NM_005477.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000165 AC: 25AN: 151784Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000585 AC: 2AN: 34200Hom.: 0 AF XY: 0.0000497 AC XY: 1AN XY: 20138
GnomAD4 exome AF: 0.0000166 AC: 20AN: 1201950Hom.: 0 Cov.: 31 AF XY: 0.0000154 AC XY: 9AN XY: 585202
GnomAD4 genome AF: 0.000165 AC: 25AN: 151892Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74254
ClinVar
Submissions by phenotype
HCN4-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 28, 2023 | The HCN4 c.302C>T variant is predicted to result in the amino acid substitution p.Ala101Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.047% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-73660310-G-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 09, 2024 | The p.A101V variant (also known as c.302C>T), located in coding exon 1 of the HCN4 gene, results from a C to T substitution at nucleotide position 302. The alanine at codon 101 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Brugada syndrome 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at