14-62707584-T-TG

Position:

• chr14-62707584-T-TG

Variant summary

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

The NM_139318.5(KCNH5):​c.2890_2891insC​(p.Gln964ProfsTer9) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000733 in 1,527,874 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: KCNH5 NM_139318.5 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.34

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 14-62707584-T-TG is Benign according to our data. Variant chr14-62707584-T-TG is described in ClinVar as [Likely_benign]. Clinvar id is 661495.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/exons	MANE	UniProt
KCNH5	NM_139318.5	c.2890_2891insC	p.Gln964ProfsTer9	frameshift_variant	11/11	ENST00000322893.12
KCNH5	NM_172375.3	c.*857_*858insC		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH5	ENST00000322893.12	c.2890_2891insC	p.Gln964ProfsTer9	frameshift_variant	11/11	1	NM_139318.5	P1
KCNH5	ENST00000420622.6	c.*857_*858insC		3_prime_UTR_variant	10/10	1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152020 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000756 AC: 104 AN: 1375738 Hom.: 0 Cov.: 29 AF XY: 0.0000683 AC XY: 46 AN XY: 673384

Gnomad4 AFR exome AF: 0.000195

Gnomad4 AMR exome AF: 0.0000300

Gnomad4 ASJ exome AF: 0.0000478

Gnomad4 EAS exome AF: 0.0000516

Gnomad4 SAS exome AF: 0.0000282

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000824

Gnomad4 OTH exome AF: 0.0000706

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74370

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000174 Hom.: 0

Bravo AF: 0.0000869

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

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: rs35940222; hg19: chr14-63174302;