14-63006474-TGG-TG

Variant names:

• chr14-63006474-TG-T
• rs752865520
• NM_139318.5:c.198-3delC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_139318.5(KCNH5):​c.198-3delC variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0000211 in 1,564,544 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: KCNH5 NM_139318.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.83

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 14-63006474-TG-T is Benign according to our data. Variant chr14-63006474-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 461389.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH5	NM_139318.5	c.198-3delC		splice_region_variant, intron_variant	Intron 2 of 10	ENST00000322893.12	NP_647479.2
KCNH5	NM_172375.3	c.198-3delC		splice_region_variant, intron_variant	Intron 2 of 9		NP_758963.1
KCNH5	XM_047431275.1	c.198-3delC		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
KCNH5	ENST00000322893.12	c.198-3delC		splice_region_variant, intron_variant	Intron 2 of 10	1	NM_139318.5	ENSP00000321427.7
KCNH5	ENST00000420622.6	c.198-3delC		splice_region_variant, intron_variant	Intron 2 of 9	1		ENSP00000395439.2
KCNH5	ENST00000394964.3	n.363-3delC		splice_region_variant, intron_variant	Intron 2 of 6	1
KCNH5	ENST00000394968.2	c.24-3delC		splice_region_variant, intron_variant	Intron 2 of 10	2		ENSP00000378419.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151262 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 31 AN: 1413166 Hom.: 0 Cov.: 23 AF XY: 0.0000184 AC XY: 13 AN XY: 704938

Gnomad4 AFR exome AF: 0.0000309

Gnomad4 AMR exome AF: 0.0000231

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000252

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151378 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 73992

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

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

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts Benign:1

Oct 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs752865520; hg19: chr14-63473192;