rs759624671
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_139318.5(KCNH5):āc.1557T>Cā(p.Ile519=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,338 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 (ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 32)
Exomes š: 0.000012 ( 1 hom. )
Consequence
KCNH5
NM_139318.5 synonymous
NM_139318.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.137
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 Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 14-62849665-A-G is Benign according to our data. Variant chr14-62849665-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 530561.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.137 with no splicing effect.
BS2
?
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNH5 | NM_139318.5 | c.1557T>C | p.Ile519= | synonymous_variant | 8/11 | ENST00000322893.12 | |
KCNH5 | NM_172375.3 | c.1557T>C | p.Ile519= | synonymous_variant | 8/10 | ||
KCNH5 | XM_047431275.1 | c.1557T>C | p.Ile519= | synonymous_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNH5 | ENST00000322893.12 | c.1557T>C | p.Ile519= | synonymous_variant | 8/11 | 1 | NM_139318.5 | P1 | |
KCNH5 | ENST00000420622.6 | c.1557T>C | p.Ile519= | synonymous_variant | 8/10 | 1 | |||
KCNH5 | ENST00000394968.2 | c.1383T>C | p.Ile461= | synonymous_variant | 8/11 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251192Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135752
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461152Hom.: 1 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 726916
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74352
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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 submitter | clinical testing | Invitae | Mar 27, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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