rs202187957

Variant names:

• chr20-44746008-C-A
• rs202187957
• NM_022358.4:c.98C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-44746008-C-A
• chr20-44746008-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022358.4(KCNK15):​c.98C>A​(p.Ala33Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,382,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. A33V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: KCNK15 NM_022358.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 2 publications found

Genes affected

KCNK15 (HGNC:13814): (potassium two pore domain channel subfamily K member 15) 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]

KCNK15-AS1 (HGNC:49901): (KCNK15 and WISP2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07616648).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022358.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK15	NM_022358.4	MANE Select	c.98C>A	p.Ala33Glu	missense	Exon 1 of 2	NP_071753.2	Q9H427
	KCNK15-AS1	NR_132377.1		n.220G>T		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK15	ENST00000372861.5	TSL:1 MANE Select	c.98C>A	p.Ala33Glu	missense	Exon 1 of 2	ENSP00000361952.3	Q9H427
	KCNK15-AS1	ENST00000427303.2	TSL:5	n.14G>T		non_coding_transcript_exon	Exon 1 of 6
	KCNK15-AS1	ENST00000445420.6	TSL:2	n.267G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1382108 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 683644

African (AFR) AF: 0.00 AC: 0 AN: 28812

American (AMR) AF: 0.00 AC: 0 AN: 34480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23500

East Asian (EAS) AF: 0.00 AC: 0 AN: 33680

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5426

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073120

Other (OTH) AF: 0.00 AC: 0 AN: 56470

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000235 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.84
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.59
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.98	T
PhyloP100		2.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.084
Sift	Benign	0.92	T
Sift4G	Benign	0.31	T
Vest4		0.33
MutPred		0.42		Gain of solvent accessibility (P = 0.0261)
MVP		0.20
ClinPred		0.29	T
GERP RS		3.1
PromoterAI		0.028	Neutral
gMVP		0.57
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs202187957; hg19: chr20-43374649; COSMIC: COSV65730087; COSMIC: COSV65730087;