rs753938626
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP6_ModerateBS2
The NM_139318.5(KCNH5):c.1847T>A(p.Ile616Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,613,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )
Consequence
KCNH5
NM_139318.5 missense
NM_139318.5 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 5.36
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, KCNH5
BP6
?
Variant 14-62779900-A-T is Benign according to our data. Variant chr14-62779900-A-T is described in ClinVar as [Benign]. Clinvar id is 581723.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAdExome4 at 51 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNH5 | NM_139318.5 | c.1847T>A | p.Ile616Asn | missense_variant | 10/11 | ENST00000322893.12 | |
KCNH5 | XM_047431275.1 | c.1831T>A | p.Ser611Thr | missense_variant | 10/10 | ||
KCNH5 | NM_172375.3 | c.1822+22429T>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNH5 | ENST00000322893.12 | c.1847T>A | p.Ile616Asn | missense_variant | 10/11 | 1 | NM_139318.5 | P1 | |
KCNH5 | ENST00000420622.6 | c.1822+22429T>A | intron_variant | 1 | |||||
KCNH5 | ENST00000394968.2 | c.1673T>A | p.Ile558Asn | missense_variant | 10/11 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248526Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134446
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GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461146Hom.: 0 Cov.: 30 AF XY: 0.0000316 AC XY: 23AN XY: 726864
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Uncertain
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Gain of catalytic residue at V612 (P = 0.0199);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at