Variant 14-63006481-GA-GAA details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000322893.12(KCNH5):c.198-10_198-9insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000454 in 1,466,026 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

KCNH5
ENST00000322893.12 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.114

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 -6 ACMG points.

BP6

Variant 14-63006481-G-GA is Benign according to our data. Variant chr14-63006481-G-GA is described in ClinVar as [Benign]. Clinvar id is 461388.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 303 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
KCNH5	NM_139318.5 linkuse as main transcript	c.198-10_198-9insT	splice_polypyrimidine_tract_variant, intron_variant	ENST00000322893.12	NP_647479.2
KCNH5	NM_172375.3 linkuse as main transcript	c.198-10_198-9insT	splice_polypyrimidine_tract_variant, intron_variant		NP_758963.1
KCNH5	XM_047431275.1 linkuse as main transcript	c.198-10_198-9insT	splice_polypyrimidine_tract_variant, intron_variant		XP_047287231.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
KCNH5	ENST00000322893.12 linkuse as main transcript	c.198-10_198-9insT	splice_polypyrimidine_tract_variant, intron_variant	1	NM_139318.5	ENSP00000321427	P1	Q8NCM2-1
KCNH5	ENST00000420622.6 linkuse as main transcript	c.198-10_198-9insT	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000395439		Q8NCM2-2
KCNH5	ENST00000394964.3 linkuse as main transcript	n.363-10_363-9insT	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1
KCNH5	ENST00000394968.2 linkuse as main transcript	c.24-10_24-9insT	splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000378419		Q8NCM2-3

Frequencies

GnomAD3 genomes

AF:

0.00201

AC:

304

AN:

151526

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00720

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000460

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:

0.000584

AC:

134

AN:

229392

Hom.:

AF XY:

0.000467

AC XY:

AN XY:

124210

show subpopulations

Gnomad AFR exome

AF:

0.00763

Gnomad AMR exome

AF:

0.000361

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000502

Gnomad NFE exome

AF:

0.0000285

Gnomad OTH exome

AF:

0.000362

GnomAD4 exome

AF:

0.000275

AC:

362

AN:

1314384

Hom.:

Cov.:

AF XY:

0.000252

AC XY:

166

AN XY:

659712

show subpopulations

Gnomad4 AFR exome

AF:

0.00789

Gnomad4 AMR exome

AF:

0.000360

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000625

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.0000679

Gnomad4 OTH exome

AF:

0.000598

GnomAD4 genome

AF:

0.00200

AC:

303

AN:

151642

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

138

AN XY:

74054

show subpopulations

Gnomad4 AFR

AF:

0.00718

Gnomad4 AMR

AF:

0.000394

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

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

Jan 30, 2024

- -

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.

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