rs749274421

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033347.2(KCNK7):​c.661G>T​(p.Gly221Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G221R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KCNK7
NM_033347.2 missense

Scores

2
5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75
Variant links:
Genes affected
KCNK7 (HGNC:6282): (potassium two pore domain channel subfamily K member 7) This gene encodes a member 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNK7NM_033347.2 linkc.661G>T p.Gly221Cys missense_variant Exon 2 of 3 ENST00000340313.5 NP_203133.1 Q9Y2U2-1
KCNK7NM_005714.2 linkc.661G>T p.Gly221Cys missense_variant Exon 2 of 2 NP_005705.1 Q9Y2U2-3A0A024R5F5
KCNK7NM_033348.2 linkc.661G>T p.Gly221Cys missense_variant Exon 2 of 4 NP_203134.1 Q9Y2U2-2A0A024R5B0
KCNK7NM_033455.2 linkc.661G>T p.Gly221Cys missense_variant Exon 2 of 3 NP_258416.1 Q9Y2U2-2A0A024R5B0Q3SYI1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNK7ENST00000340313.5 linkc.661G>T p.Gly221Cys missense_variant Exon 2 of 3 1 NM_033347.2 ENSP00000344820.5 Q9Y2U2-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459704
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726228
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.89
.;.;.;D
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.69
.;T;T;T
M_CAP
Benign
0.045
D
MetaRNN
Uncertain
0.46
T;T;T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Uncertain
2.2
M;M;M;M
PrimateAI
Benign
0.26
T
PROVEAN
Pathogenic
-6.8
D;D;D;D
REVEL
Benign
0.10
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.0060
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.43
MutPred
0.47
Loss of disorder (P = 0.0048);Loss of disorder (P = 0.0048);Loss of disorder (P = 0.0048);Loss of disorder (P = 0.0048);
MVP
0.56
MPC
0.17
ClinPred
0.89
D
GERP RS
-0.59
Varity_R
0.47
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65361004; API