rs1555351942

Variant names:

• chr14-62708166-G-T
• rs1555351942
• NM_139318.5:c.2309C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-62708166-G-T
• chr14-62708166-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139318.5(KCNH5):​c.2309C>A​(p.Thr770Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNH5 NM_139318.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 4.74
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13560727).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH5	NM_139318.5	MANE Select	c.2309C>A	p.Thr770Asn	missense	Exon 11 of 11	NP_647479.2
	KCNH5	NM_172375.3		c.*276C>A		3_prime_UTR	Exon 10 of 10	NP_758963.1	Q8NCM2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH5	ENST00000322893.12	TSL:1 MANE Select	c.2309C>A	p.Thr770Asn	missense	Exon 11 of 11	ENSP00000321427.7	Q8NCM2-1
	KCNH5	ENST00000420622.6	TSL:1	c.*276C>A		3_prime_UTR	Exon 10 of 10	ENSP00000395439.2	Q8NCM2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental and epileptic encephalopathy (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.0060	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.099
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	0.76	D
MutationAssessor	Benign	0.34	N
PhyloP100		4.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.59	N
REVEL	Uncertain	0.34
Sift	Benign	0.34	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.29		Gain of catalytic residue at Y767 (P = 0.0174)
MVP		0.71
MPC		0.13
ClinPred		0.69	D
GERP RS		5.4
Varity_R		0.16
gMVP		0.32
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: rs1555351942; hg19: chr14-63174884;