20-44746015-C-G

Variant names:

• chr20-44746015-C-G
• rs952591436
• NM_022358.4:c.105C>G

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.105C>G​(p.Ser35Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,376,088 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: KCNK15 NM_022358.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 0 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=0.08489889).

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.105C>G	p.Ser35Arg	missense	Exon 1 of 2	NP_071753.2	Q9H427
	KCNK15-AS1	NR_132377.1		n.213G>C		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.105C>G	p.Ser35Arg	missense	Exon 1 of 2	ENSP00000361952.3	Q9H427
	KCNK15-AS1	ENST00000427303.2	TSL:5	n.7G>C		non_coding_transcript_exon	Exon 1 of 6
	KCNK15-AS1	ENST00000445420.6	TSL:2	n.260G>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 155884 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1376088 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 680710

African (AFR) AF: 0.00 AC: 0 AN: 28654

American (AMR) AF: 0.00 AC: 0 AN: 34014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23392

East Asian (EAS) AF: 0.00 AC: 0 AN: 33144

South Asian (SAS) AF: 0.00 AC: 0 AN: 76824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5396

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1069472

Other (OTH) AF: 0.00 AC: 0 AN: 56128

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.53
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.95
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.98	T
PhyloP100		1.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.039
Sift	Benign	0.60	T
Sift4G	Benign	0.48	T
Vest4		0.11
MutPred		0.40		Loss of phosphorylation at S35 (P = 0.0297)
MVP		0.17
ClinPred		0.051	T
GERP RS		0.83
PromoterAI		0.069	Neutral
gMVP		0.50
Mutation Taster		=81/19	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: rs952591436; hg19: chr20-43374656;