chr1-155284023-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_020897.3(HCN3):c.758A>C(p.Asn253Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,906 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.758A>C | p.Asn253Thr | missense_variant | Exon 3 of 8 | 1 | NM_020897.3 | ENSP00000357342.3 | ||
HCN3 | ENST00000496230.5 | n.650A>C | non_coding_transcript_exon_variant | Exon 3 of 8 | 2 | |||||
HCN3 | ENST00000467204.1 | n.304-516A>C | intron_variant | Intron 1 of 4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152044Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251474Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135914
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461862Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727244
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152044Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74240
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.758A>C (p.N253T) alteration is located in exon 3 (coding exon 3) of the HCN3 gene. This alteration results from a A to C substitution at nucleotide position 758, causing the asparagine (N) at amino acid position 253 to be replaced by a threonine (T). 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