14-62708387-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_139318.5(KCNH5):c.2088G>A(p.Val696Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,613,142 control chromosomes in the GnomAD database, including 1,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 118 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1241 hom. )

Consequence

KCNH5
NM_139318.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.192

Publications

6 publications found

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 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

KCNH5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 14-62708387-C-T is Benign according to our data. Variant chr14-62708387-C-T is described in ClinVar as Benign. ClinVar VariationId is 416125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.192 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH5	NM_139318.5 link	c.2088G>A	p.Val696Val	synonymous_variant	Exon 11 of 11	ENST00000322893.12	NP_647479.2
KCNH5	NM_172375.3 link	c.*55G>A		3_prime_UTR_variant	Exon 10 of 10		NP_758963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000322893.12 link	c.2088G>A	p.Val696Val	synonymous_variant	Exon 11 of 11	1	NM_139318.5	ENSP00000321427.7
KCNH5	ENST00000420622.6 link	c.*55G>A		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000395439.2

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4650

AN:

152100

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00618

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0679

Gnomad FIN

AF:

0.0733

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0415

Gnomad OTH

AF:

0.0292

GnomAD2 exomes

AF:

0.0347

AC:

8697

AN:

250560

AF XY:

0.0361

show subpopulations

Gnomad AFR exome

AF:

0.00517

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.00586

Gnomad EAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.0747

Gnomad NFE exome

AF:

0.0396

Gnomad OTH exome

AF:

0.0295

GnomAD4 exome

AF:

0.0371

AC:

54211

AN:

1460924

Hom.:

1241

Cov.:

AF XY:

0.0378

AC XY:

27460

AN XY:

726772

show subpopulations

African (AFR)

AF:

0.00448

AC:

150

AN:

33480

American (AMR)

AF:

0.0122

AC:

544

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00643

AC:

168

AN:

26134

East Asian (EAS)

AF:

0.00340

AC:

135

AN:

39694

South Asian (SAS)

AF:

0.0609

AC:

5254

AN:

86252

European-Finnish (FIN)

AF:

0.0716

AC:

3767

AN:

52638

Middle Eastern (MID)

AF:

0.00452

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0380

AC:

42293

AN:

1111862

Other (OTH)

AF:

0.0310

AC:

1874

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2674

5348

8021

10695

13369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1550

3100

4650

6200

7750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0306

AC:

4655

AN:

152218

Hom.:

118

Cov.:

AF XY:

0.0325

AC XY:

2416

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00616

AC:

256

AN:

41546

American (AMR)

AF:

0.0203

AC:

311

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00662

AC:

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5164

South Asian (SAS)

AF:

0.0680

AC:

328

AN:

4826

European-Finnish (FIN)

AF:

0.0733

AC:

777

AN:

10600

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0415

AC:

2819

AN:

67994

Other (OTH)

AF:

0.0313

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

237

473

710

946

1183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0345

Hom.:

413

Bravo

AF:

0.0237

Asia WGS

AF:

0.0600

AC:

209

AN:

3478

EpiCase

AF:

0.0327

EpiControl

AF:

0.0328

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

KCNH5-related disorder

Benign:1

Mar 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.2

(source)

DANN

Benign

0.69

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over