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rs368953680

chr14-62707522-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_139318.5(KCNH5):c.2953G>T(p.Glu985Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000673 in 1,442,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

KCNH5
NM_139318.5 stop_gained

Scores

5
1
1

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.66
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM4
?
    PM4 - Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants
Stoplost variant in NM_139318.5 Downstream stopcodon found after 315 codons.
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-62707522-C-A is Benign according to our data. Variant chr14-62707522-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 530640.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KCNH5NM_139318.5 linkuse as main transcriptc.2953G>T p.Glu985Ter stop_gained 11/11 ENST00000322893.12
KCNH5NM_172375.3 linkuse as main transcriptc.*920G>T 3_prime_UTR_variant 10/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KCNH5ENST00000322893.12 linkuse as main transcriptc.2953G>T p.Glu985Ter stop_gained 11/111 NM_139318.5 P1Q8NCM2-1
KCNH5ENST00000420622.6 linkuse as main transcript downstream_gene_variant 1 Q8NCM2-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000151
AC:
23
AN:
152018
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000108
AC:
18
AN:
166298
Hom.:
0
AF XY:
0.0000795
AC XY:
7
AN XY:
88066
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000454
Gnomad ASJ exome
AF:
0.00154
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000362
Gnomad OTH exome
AF:
0.000555
GnomAD4 exome
AF:
0.0000574
AC:
74
AN:
1289904
Hom.:
0
Cov.:
27
AF XY:
0.0000559
AC XY:
35
AN XY:
625822
show subpopulations
Gnomad4 AFR exome
AF:
0.0000343
Gnomad4 AMR exome
AF:
0.000629
Gnomad4 ASJ exome
AF:
0.000861
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000780
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000264
Gnomad4 OTH exome
AF:
0.000151
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000151
AC:
23
AN:
152128
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.000131
Hom.:
0
Bravo
AF:
0.000238
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
?
    Exome Aggregation Consortium database
AF:
0.000111
AC:
13

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 submitterclinical testingInvitaeNov 24, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.65
Cadd
Pathogenic
38
Dann
Uncertain
1.0
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.94
FATHMM_MKL
Pathogenic
0.99
D
MutationTaster
Benign
1.0
D
Vest4
0.63
GERP RS
5.4

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.

Other links and lift over

dbSNP: rs368953680; hg19: chr14-63174240; API