Variant rs753938626 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP6_ModerateBS2

The ENST00000322893.12(KCNH5):c.1847T>A(p.Ile616Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,613,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

KCNH5
ENST00000322893.12 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.36

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KCNH5. . Gene score misZ 2.509 (greater than the threshold 3.09). Trascript score misZ 3.7308 (greater than threshold 3.09). GenCC has associacion of gene with infantile-onset epilepsy.

BP6

Variant 14-62779900-A-T is Benign according to our data. Variant chr14-62779900-A-T is described in ClinVar as [Benign]. Clinvar id is 581723.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 51 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KCNH5	NM_139318.5 linkuse as main transcript	c.1847T>A	p.Ile616Asn	missense_variant	10/11	ENST00000322893.12	NP_647479.2
KCNH5	XM_047431275.1 linkuse as main transcript	c.1831T>A	p.Ser611Thr	missense_variant	10/10		XP_047287231.1
KCNH5	NM_172375.3 linkuse as main transcript	c.1822+22429T>A		intron_variant			NP_758963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000322893.12 linkuse as main transcript	c.1847T>A	p.Ile616Asn	missense_variant	10/11	1	NM_139318.5	ENSP00000321427	P1	Q8NCM2-1
KCNH5	ENST00000420622.6 linkuse as main transcript	c.1822+22429T>A		intron_variant		1		ENSP00000395439		Q8NCM2-2
KCNH5	ENST00000394968.2 linkuse as main transcript	c.1673T>A	p.Ile558Asn	missense_variant	10/11	2		ENSP00000378419		Q8NCM2-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248526

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134446

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1461146

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000487

Hom.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Benign

0.84

DEOGEN2

Uncertain

0.45

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

0.047

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.075

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Uncertain

0.29

MutationAssessor

Benign

-0.030

N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.19

N;N

REVEL

Uncertain

0.51

Sift

Benign

0.58

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0

B;B

Vest4

0.85

MutPred

0.32

Gain of catalytic residue at V612 (P = 0.0199);.;

MVP

0.57

MPC

1.7

ClinPred

0.45

GERP RS

5.6

Varity_R

0.36

gMVP

0.92

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over