chr19-590366-G-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001194.4(HCN2):c.421G>T(p.Ala141Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00746 in 1,153,368 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A141V) has been classified as Likely benign.
Frequency
Consequence
NM_001194.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN2 | NM_001194.4 | c.421G>T | p.Ala141Ser | missense_variant | 1/8 | ENST00000251287.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN2 | ENST00000251287.3 | c.421G>T | p.Ala141Ser | missense_variant | 1/8 | 1 | NM_001194.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00554 AC: 818AN: 147642Hom.: 7 Cov.: 31
GnomAD3 exomes AF: 0.00743 AC: 15AN: 2018Hom.: 0 AF XY: 0.00611 AC XY: 7AN XY: 1146
GnomAD4 exome AF: 0.00774 AC: 7785AN: 1005616Hom.: 43 Cov.: 31 AF XY: 0.00787 AC XY: 3735AN XY: 474724
GnomAD4 genome AF: 0.00554 AC: 818AN: 147752Hom.: 7 Cov.: 31 AF XY: 0.00511 AC XY: 368AN XY: 72056
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 25, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at