chr20-44745926-G-C

Position:

• chr20-44745926-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022358.4(KCNK15):​c.16G>C​(p.Val6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 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)
• Consequence: KCNK15 NM_022358.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90

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

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=0.17731452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK15	NM_022358.4	c.16G>C	p.Val6Leu	missense_variant	1/2	ENST00000372861.5	NP_071753.2
KCNK15-AS1	NR_132377.1	n.263+39C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK15	ENST00000372861.5	c.16G>C	p.Val6Leu	missense_variant	1/2	1	NM_022358.4	ENSP00000361952	P1
KCNK15-AS1	ENST00000445420.5	n.31+39C>G		intron_variant, non_coding_transcript_variant		2
KCNK15-AS1	ENST00000427303.2	n.57+39C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2024

The c.16G>C (p.V6L) alteration is located in exon 1 (coding exon 1) of the KCNK15 gene. This alteration results from a G to C substitution at nucleotide position 16, causing the valine (V) at amino acid position 6 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
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Uncertain	0.98
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.89	D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.063
Sift	Benign	0.15	T
Sift4G	Benign	0.12	T
Vest4		0.14
MutPred		0.36		Loss of helix (P = 0.079);
MVP		0.25
ClinPred		0.26	T
GERP RS		4.1
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-43374567;