rs142252600

chr14-62987093-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_139318.5(KCNH5):c.528T>C(p.His176=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000661 in 1,613,086 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (1 hom.)
• Consequence: KCNH5 NM_139318.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.05

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 14-62987093-A-G is Benign according to our data. Variant chr14-62987093-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 416116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 72 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNH5	NM_139318.5	c.528T>C	p.His176=	synonymous_variant	5/11	ENST00000322893.12
KCNH5	NM_172375.3	c.528T>C	p.His176=	synonymous_variant	5/10
KCNH5	XM_047431275.1	c.528T>C	p.His176=	synonymous_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNH5	ENST00000322893.12	c.528T>C	p.His176=	synonymous_variant	5/11	1	NM_139318.5	P1
KCNH5	ENST00000420622.6	c.528T>C	p.His176=	synonymous_variant	5/10	1
KCNH5	ENST00000394964.3	n.693T>C		non_coding_transcript_exon_variant	5/7	1
KCNH5	ENST00000394968.2	c.354T>C	p.His118=	synonymous_variant	5/11	2

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000823

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000275 AC: 69 AN: 251244 Hom.: 0 AF XY: 0.000302 AC XY: 41 AN XY: 135776

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000546

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000680 AC: 994 AN: 1460890 Hom.: 1 Cov.: 30 AF XY: 0.000676 AC XY: 491 AN XY: 726824

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000869

Gnomad4 OTH exome AF: 0.000331

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.000403 AC XY: 30 AN XY: 74352

Gnomad4 AFR AF: 0.000338

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000823

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000687 Hom.: 0

Bravo AF: 0.000389

EpiCase AF: 0.000655

EpiControl AF: 0.000593

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 27, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	7.5
Dann	Benign	0.62

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: rs142252600; hg19: chr14-63453811; COSMIC: COSV59755871;