rs752865520

Variant names:

• chr14-63006474-TGG-T
• rs752865520
• NM_139318.5:c.198-4_198-3delCC

Your query was ambiguous. Multiple possible variants found:

• chr14-63006474-TGG-T
• chr14-63006474-TGG-TG
• chr14-63006474-TGG-TGGG

Variant summary

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

The NM_139318.5(KCNH5):​c.198-4_198-3delCC variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000000708 in 1,413,280 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: KCNH5 NM_139318.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.83
• Publications: 0 publications found

Genes affected

KCNH5 (HGNC:6254): (potassium voltage-gated channel subfamily H member 5) This gene encodes a member of voltage-gated potassium channels. Members of this family have diverse functions, including regulating neurotransmitter and hormone release, cardiac function, and cell volume. This protein is an outward-rectifying, noninactivating channel. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

KCNH5 Gene-Disease associations (from GenCC):

• infantile-onset epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy 112

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
KCNH5	NM_139318.5	c.198-4_198-3delCC		splice_region_variant, intron_variant	Intron 2 of 10	ENST00000322893.12	NP_647479.2
KCNH5	NM_172375.3	c.198-4_198-3delCC		splice_region_variant, intron_variant	Intron 2 of 9		NP_758963.1
KCNH5	XM_047431275.1	c.198-4_198-3delCC		splice_region_variant, intron_variant	Intron 2 of 9		XP_047287231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000322893.12	c.198-4_198-3delCC		splice_region_variant, intron_variant	Intron 2 of 10	1	NM_139318.5	ENSP00000321427.7
KCNH5	ENST00000420622.6	c.198-4_198-3delCC		splice_region_variant, intron_variant	Intron 2 of 9	1		ENSP00000395439.2
KCNH5	ENST00000394964.3	n.363-4_363-3delCC		splice_region_variant, intron_variant	Intron 2 of 6	1
KCNH5	ENST00000394968.2	c.24-4_24-3delCC		splice_region_variant, intron_variant	Intron 2 of 10	2		ENSP00000378419.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1413280 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 704994

⚠️ 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: 32386

American (AMR) AF: 0.00 AC: 0 AN: 43272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25624

East Asian (EAS) AF: 0.00 AC: 0 AN: 39336

South Asian (SAS) AF: 0.00 AC: 0 AN: 83428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 9.33e-7 AC: 1 AN: 1072264

Other (OTH) AF: 0.00 AC: 0 AN: 58626

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.8

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: rs752865520; hg19: chr14-63473192;