dbSNP rs12239421: HCN3:c.1237-147C>A (chr1-155285577-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020897.3(HCN3):c.1237-147C>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HCN3
NM_020897.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.415

Publications

1 publications found

Variant links:

Genes affected

HCN3 (HGNC:19183): (hyperpolarization activated cyclic nucleotide gated potassium channel 3) This gene encodes a multi-pass membrane protein that functions as a voltage gated cation channel. The encoded protein is a member of a family of closely related cyclic adenosine monophosphate-binding channel proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

HCN3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCN3	NM_020897.3 link	c.1237-147C>A		intron_variant	Intron 5 of 7	ENST00000368358.4	NP_065948.1	Q9P1Z3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HCN3	ENST00000368358.4 link	c.1237-147C>A	intron_variant	Intron 5 of 7	1	NM_020897.3	ENSP00000357342.3	Q9P1Z3
HCN3	ENST00000467204.1 link	n.669+266C>A	intron_variant	Intron 3 of 4	5
HCN3	ENST00000496230.5 link	n.1532-147C>A	intron_variant	Intron 4 of 7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

998498

Hom.:

AF XY:

0.00

AC XY:

AN XY:

496872

African (AFR)

AF:

0.00

AC:

AN:

22912

American (AMR)

AF:

0.00

AC:

AN:

22836

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17492

East Asian (EAS)

AF:

0.00

AC:

AN:

34056

South Asian (SAS)

AF:

0.00

AC:

AN:

58666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3076

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

760608

Other (OTH)

AF:

0.00

AC:

AN:

44184

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.70

(source)

DANN

Benign

0.70

PhyloP100

-0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over