rs10136789

Variant names:

• chr14-62889535-T-C
• rs10136789
• NM_139318.5:c.1370-39683A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139318.5(KCNH5):​c.1370-39683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,220 control chromosomes in the GnomAD database, including 1,931 homozygotes. 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: 𝑓 0.14 (1931 hom., cov: 32)
• Consequence: KCNH5 NM_139318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139318.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH5	NM_139318.5	MANE Select	c.1370-39683A>G		intron	N/A	NP_647479.2
	KCNH5	NM_172375.3		c.1370-39683A>G		intron	N/A	NP_758963.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH5	ENST00000322893.12	TSL:1 MANE Select	c.1370-39683A>G		intron	N/A	ENSP00000321427.7
	KCNH5	ENST00000420622.6	TSL:1	c.1370-39683A>G		intron	N/A	ENSP00000395439.2
	KCNH5	ENST00000394968.2	TSL:2	c.1196-39683A>G		intron	N/A	ENSP00000378419.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21869 AN: 152100 Hom.: 1926 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.144 AC: 21895 AN: 152220 Hom.: 1931 Cov.: 32 AF XY: 0.140 AC XY: 10421 AN XY: 74428

African (AFR) AF: 0.249 AC: 10318 AN: 41502

American (AMR) AF: 0.0847 AC: 1296 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 176 AN: 3468

East Asian (EAS) AF: 0.119 AC: 617 AN: 5180

South Asian (SAS) AF: 0.0580 AC: 280 AN: 4828

European-Finnish (FIN) AF: 0.116 AC: 1228 AN: 10604

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7647 AN: 68012

Other (OTH) AF: 0.119 AC: 252 AN: 2114

Alfa AF: 0.116 Hom.: 2237

Bravo AF: 0.148

Asia WGS AF: 0.102 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.035
DANN	Benign	0.27
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs10136789; hg19: chr14-63356253;