17-7925686-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004732.4(KCNAB3):c.535G>A(p.Glu179Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,614,016 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
KCNAB3
NM_004732.4 missense
NM_004732.4 missense
Scores
8
6
5
Clinical Significance
Conservation
PhyloP100: 6.89
Genes affected
KCNAB3 (HGNC:6230): (potassium voltage-gated channel subfamily A regulatory beta subunit 3) This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. The encoded protein is one of the beta subunits, which are auxiliary proteins associating with functional Kv-alpha subunits. The encoded protein forms a heterodimer with the potassium voltage-gated channel, shaker-related subfamily, member 5 gene product and regulates the activity of the alpha subunit. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.773
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNAB3 | NM_004732.4 | c.535G>A | p.Glu179Lys | missense_variant | 7/14 | ENST00000303790.3 | NP_004723.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNAB3 | ENST00000303790.3 | c.535G>A | p.Glu179Lys | missense_variant | 7/14 | 1 | NM_004732.4 | ENSP00000302719 | P1 | |
KCNAB3 | ENST00000570587.5 | c.*776G>A | 3_prime_UTR_variant, NMD_transcript_variant | 7/15 | 1 | ENSP00000458237 | ||||
KCNAB3 | ENST00000576981.1 | n.86G>A | non_coding_transcript_exon_variant | 2/6 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152130Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251496Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135922
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727246
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152130Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74310
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2023 | The c.535G>A (p.E179K) alteration is located in exon 7 (coding exon 7) of the KCNAB3 gene. This alteration results from a G to A substitution at nucleotide position 535, causing the glutamic acid (E) at amino acid position 179 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.0016);
MVP
MPC
ClinPred
D
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