1-233614405-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002245.4(KCNK1):​c.234C>G​(p.Phe78Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,459,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

KCNK1
NM_002245.4 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80
Variant links:
Genes affected
KCNK1 (HGNC:6272): (potassium two pore domain channel subfamily K member 1) This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. The product of this gene has not been shown to be a functional channel, however, it may require other non-pore-forming proteins for activity. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1774337).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNK1NM_002245.4 linkc.234C>G p.Phe78Leu missense_variant Exon 1 of 3 ENST00000366621.8 NP_002236.1 O00180A0A024R3T2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNK1ENST00000366621.8 linkc.234C>G p.Phe78Leu missense_variant Exon 1 of 3 1 NM_002245.4 ENSP00000355580.3 O00180

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000409
AC:
1
AN:
244518
Hom.:
0
AF XY:
0.00000753
AC XY:
1
AN XY:
132840
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:
0.00000908
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000151
AC:
22
AN:
1459778
Hom.:
0
Cov.:
34
AF XY:
0.0000124
AC XY:
9
AN XY:
726008
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.0000171
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 28, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.234C>G (p.F78L) alteration is located in exon 1 (coding exon 1) of the KCNK1 gene. This alteration results from a C to G substitution at nucleotide position 234, causing the phenylalanine (F) at amino acid position 78 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Benign
-0.023
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.32
T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.33
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.066
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.19
Sift
Benign
0.32
T
Sift4G
Benign
0.89
T
Polyphen
0.012
B
Vest4
0.41
MutPred
0.49
Loss of helix (P = 0.0072);
MVP
0.70
MPC
0.44
ClinPred
0.32
T
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.85
gMVP
0.83

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: rs1264295196; hg19: chr1-233750151; API