chr20-44746015-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_022358.4(KCNK15):​c.105C>T​(p.Ser35Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,376,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: KCNK15 NM_022358.4 synonymous
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=1.03 with no splicing effect.

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>T	p.Ser35Ser	synonymous	Exon 1 of 2	NP_071753.2	Q9H427
	KCNK15-AS1	NR_132377.1		n.213G>A		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>T	p.Ser35Ser	synonymous	Exon 1 of 2	ENSP00000361952.3	Q9H427
	KCNK15-AS1	ENST00000427303.2	TSL:5	n.7G>A		non_coding_transcript_exon	Exon 1 of 6
	KCNK15-AS1	ENST00000445420.6	TSL:2	n.260G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000218 AC: 3 AN: 1376080 Hom.: 0 Cov.: 30 AF XY: 0.00000441 AC XY: 3 AN XY: 680706

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 49060

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

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1069468

Other (OTH) AF: 0.0000178 AC: 1 AN: 56128

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00250614), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.7
DANN	Benign	0.91
PhyloP100		1.0
PromoterAI		0.0062	Neutral

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;