12-49557497-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_012284.3(KCNH3):c.2796C>T(p.Ser932=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,611,532 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0088 ( 17 hom., cov: 32)
Exomes 𝑓: 0.00094 ( 18 hom. )
Consequence
KCNH3
NM_012284.3 synonymous
NM_012284.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.118
Genes affected
KCNH3 (HGNC:6252): (potassium voltage-gated channel subfamily H member 3) The protein encoded by this gene is a voltage-gated potassium channel alpha subunit predominantly expressed in the forebrain. Studies in mice have found that cognitive function increases when this gene is knocked out. In humans, the encoded protein has been shown to be capable of binding glycoprotein 120 of the human immunodeficiency virus type 1 (HIV-1) envelope. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]
MCRS1 (HGNC:6960): (microspherule protein 1) Enables RNA binding activity and telomerase inhibitor activity. Involved in histone H4 acetylation; negative regulation of DNA metabolic process; and positive regulation of protein localization to nucleolus. Located in cytoplasm; nucleolus; and nucleoplasm. Part of Ino80 complex; MLL1 complex; and histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 12-49557497-C-T is Benign according to our data. Variant chr12-49557497-C-T is described in ClinVar as [Benign]. Clinvar id is 735166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.118 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00883 (1345/152338) while in subpopulation AFR AF= 0.0303 (1259/41576). AF 95% confidence interval is 0.0289. There are 17 homozygotes in gnomad4. There are 670 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1345 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNH3 | NM_012284.3 | c.2796C>T | p.Ser932= | synonymous_variant | 15/15 | ENST00000257981.7 | NP_036416.1 | |
KCNH3 | NM_001314030.2 | c.2616C>T | p.Ser872= | synonymous_variant | 15/15 | NP_001300959.1 | ||
KCNH3 | XM_011538085.3 | c.2829C>T | p.Ser943= | synonymous_variant | 15/15 | XP_011536387.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNH3 | ENST00000257981.7 | c.2796C>T | p.Ser932= | synonymous_variant | 15/15 | 1 | NM_012284.3 | ENSP00000257981 | P1 | |
MCRS1 | ENST00000551598.5 | c.430-747G>A | intron_variant | 5 | ENSP00000448947 | |||||
KCNH3 | ENST00000548675.1 | n.526C>T | non_coding_transcript_exon_variant | 3/3 | 3 | |||||
KCNH3 | ENST00000649994.1 | c.*2406C>T | 3_prime_UTR_variant, NMD_transcript_variant | 16/16 | ENSP00000497890 |
Frequencies
GnomAD3 genomes AF: 0.00880 AC: 1340AN: 152220Hom.: 17 Cov.: 32
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GnomAD3 exomes AF: 0.00257 AC: 637AN: 247758Hom.: 4 AF XY: 0.00198 AC XY: 266AN XY: 134396
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GnomAD4 exome AF: 0.000940 AC: 1372AN: 1459194Hom.: 18 Cov.: 33 AF XY: 0.000851 AC XY: 618AN XY: 726040
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GnomAD4 genome AF: 0.00883 AC: 1345AN: 152338Hom.: 17 Cov.: 32 AF XY: 0.00899 AC XY: 670AN XY: 74494
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 10, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at