Variant rs374202650 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_139318.5(KCNH5):c.550-9C>T 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 0.0000298 in 1,613,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

KCNH5
NM_139318.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001215

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.13

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 14-62981273-G-A is Benign according to our data. Variant chr14-62981273-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2713391.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
KCNH5	NM_139318.5 linkuse as main transcript	c.550-9C>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000322893.12	NP_647479.2
KCNH5	NM_172375.3 linkuse as main transcript	c.550-9C>T	splice_polypyrimidine_tract_variant, intron_variant		NP_758963.1
KCNH5	XM_047431275.1 linkuse as main transcript	c.550-9C>T	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.550-9C>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_139318.5	ENSP00000321427	P1	Q8NCM2-1
KCNH5	ENST00000420622.6 linkuse as main transcript	c.550-9C>T	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000395439		Q8NCM2-2
KCNH5	ENST00000394964.3 linkuse as main transcript	n.715-9C>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1
KCNH5	ENST00000394968.2 linkuse as main transcript	c.376-9C>T	splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000378419		Q8NCM2-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000567

AC:

AN:

246864

Hom.:

AF XY:

0.0000597

AC XY:

AN XY:

134048

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:

0.000459

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1460932

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 09, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.0

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0060

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