rs1333592164

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020897.3(HCN3):​c.883G>A​(p.Gly295Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,612,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G295C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

HCN3
NM_020897.3 missense

Scores

2
6
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.86
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29568425).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HCN3NM_020897.3 linkc.883G>A p.Gly295Ser missense_variant Exon 4 of 8 ENST00000368358.4 NP_065948.1 Q9P1Z3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HCN3ENST00000368358.4 linkc.883G>A p.Gly295Ser missense_variant Exon 4 of 8 1 NM_020897.3 ENSP00000357342.3 Q9P1Z3
HCN3ENST00000467204.1 linkn.316G>A non_coding_transcript_exon_variant Exon 2 of 5 5
HCN3ENST00000496230.5 linkn.1178G>A non_coding_transcript_exon_variant Exon 3 of 8 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152238
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250726
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135468
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000480
AC:
7
AN:
1459822
Hom.:
0
Cov.:
31
AF XY:
0.00000689
AC XY:
5
AN XY:
726144
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152238
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
26
DANN
Uncertain
0.98
DEOGEN2
Benign
0.36
T
Eigen
Benign
-0.11
Eigen_PC
Benign
0.12
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Uncertain
0.093
D
MetaRNN
Benign
0.30
T
MetaSVM
Uncertain
0.36
D
MutationAssessor
Benign
0.64
N
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-2.0
N
REVEL
Uncertain
0.54
Sift
Benign
0.57
T
Sift4G
Benign
0.72
T
Polyphen
0.060
B
Vest4
0.37
MutPred
0.25
Gain of disorder (P = 0.0546);
MVP
0.92
MPC
0.61
ClinPred
0.49
T
GERP RS
5.3
Varity_R
0.22
gMVP
0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1333592164; hg19: chr1-155254342; API