6-39194301-C-T

Variant summary

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

The NM_003740.4(KCNK5):​c.502G>A​(p.Val168Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,613,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

KCNK5
NM_003740.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0220
Variant links:
Genes affected
KCNK5 (HGNC:6280): (potassium two pore domain channel subfamily K member 5) This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. The message for this gene is mainly expressed in the cortical distal tubules and collecting ducts of the kidney. The protein is highly sensitive to external pH and this, in combination with its expression pattern, suggests it may play an important role in renal potassium transport. [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=0.084560364).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KCNK5NM_003740.4 linkuse as main transcriptc.502G>A p.Val168Met missense_variant 4/5 ENST00000359534.4
KCNK5XM_005249456.2 linkuse as main transcriptc.493G>A p.Val165Met missense_variant 4/5
KCNK5XM_006715235.2 linkuse as main transcriptc.-45G>A 5_prime_UTR_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KCNK5ENST00000359534.4 linkuse as main transcriptc.502G>A p.Val168Met missense_variant 4/51 NM_003740.4 P1

Frequencies

GnomAD3 genomes
AF:
0.000243
AC:
37
AN:
152120
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000124
AC:
31
AN:
250322
Hom.:
0
AF XY:
0.000148
AC XY:
20
AN XY:
135262
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000377
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000928
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000142
AC:
207
AN:
1461088
Hom.:
0
Cov.:
32
AF XY:
0.000135
AC XY:
98
AN XY:
726830
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000358
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000169
Gnomad4 NFE exome
AF:
0.000162
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000243
AC:
37
AN:
152120
Hom.:
0
Cov.:
32
AF XY:
0.000256
AC XY:
19
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.0000966
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000116
Hom.:
0
Bravo
AF:
0.000257
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.000115
AC:
14
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 12, 2022The c.502G>A (p.V168M) alteration is located in exon 4 (coding exon 4) of the KCNK5 gene. This alteration results from a G to A substitution at nucleotide position 502, causing the valine (V) at amino acid position 168 to be replaced by a methionine (M). 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
Benign
0.093
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.34
N
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.085
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L
MutationTaster
Benign
0.64
N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.50
N
REVEL
Benign
0.042
Sift
Uncertain
0.018
D
Sift4G
Benign
0.097
T
Polyphen
0.26
B
Vest4
0.24
MVP
0.20
MPC
1.1
ClinPred
0.044
T
GERP RS
-1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.040
gMVP
0.53

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: rs751933589; hg19: chr6-39162077; API