14-63006474-TGG-TGGG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_139318.5(KCNH5):​c.198-3dupC variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000055 in 1,564,528 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

KCNH5
NM_139318.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.83
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6
Variant 14-63006474-T-TG is Benign according to our data. Variant chr14-63006474-T-TG is described in ClinVar as [Benign]. Clinvar id is 1170383.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNH5NM_139318.5 linkc.198-3dupC splice_region_variant, intron_variant Intron 2 of 10 ENST00000322893.12 NP_647479.2 Q8NCM2-1
KCNH5NM_172375.3 linkc.198-3dupC splice_region_variant, intron_variant Intron 2 of 9 NP_758963.1 Q8NCM2-2
KCNH5XM_047431275.1 linkc.198-3dupC 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
KCNH5ENST00000322893.12 linkc.198-3_198-2insC splice_region_variant, intron_variant Intron 2 of 10 1 NM_139318.5 ENSP00000321427.7 Q8NCM2-1
KCNH5ENST00000420622.6 linkc.198-3_198-2insC splice_region_variant, intron_variant Intron 2 of 9 1 ENSP00000395439.2 Q8NCM2-2
KCNH5ENST00000394964.3 linkn.363-3_363-2insC splice_region_variant, intron_variant Intron 2 of 6 1
KCNH5ENST00000394968.2 linkc.24-3_24-2insC splice_region_variant, intron_variant Intron 2 of 10 2 ENSP00000378419.1 Q8NCM2-3

Frequencies

GnomAD3 genomes
AF:
0.0000529
AC:
8
AN:
151262
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000885
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000552
AC:
78
AN:
1413266
Hom.:
0
Cov.:
23
AF XY:
0.0000468
AC XY:
33
AN XY:
704984
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000429
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.0000240
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000569
Gnomad4 OTH exome
AF:
0.0000512
GnomAD4 genome
AF:
0.0000529
AC:
8
AN:
151262
Hom.:
0
Cov.:
33
AF XY:
0.0000406
AC XY:
3
AN XY:
73866
show subpopulations
Gnomad4 AFR
AF:
0.0000243
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000885
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts Benign:1
Oct 28, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

KCNH5-related disorder Benign:1
Oct 14, 2020
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely 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

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.

Other links and lift over

dbSNP: rs752865520; hg19: chr14-63473192; API