rs1135401955
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3PP5
The NM_019842.4(KCNQ5):c.434T>G(p.Val145Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
KCNQ5
NM_019842.4 missense
NM_019842.4 missense
Scores
13
3
2
Clinical Significance
Conservation
PhyloP100: 5.91
Genes affected
KCNQ5 (HGNC:6299): (potassium voltage-gated channel subfamily Q member 5) This gene is a member of the KCNQ potassium channel gene family that is differentially expressed in subregions of the brain and in skeletal muscle. The protein encoded by this gene yields currents that activate slowly with depolarization and can form heteromeric channels with the protein encoded by the KCNQ3 gene. Currents expressed from this protein have voltage dependences and inhibitor sensitivities in common with M-currents. They are also inhibited by M1 muscarinic receptor activation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, KCNQ5
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.792
PP5
?
Variant 6-73003943-T-G is Pathogenic according to our data. Variant chr6-73003943-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 431385.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ5 | NM_019842.4 | c.434T>G | p.Val145Gly | missense_variant | 2/14 | ENST00000370398.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ5 | ENST00000370398.6 | c.434T>G | p.Val145Gly | missense_variant | 2/14 | 1 | NM_019842.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Intellectual disability, autosomal dominant 46 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 26, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;L;.;.;.;.;.;L;L;L
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D;D;D;D;D;D;D;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;D;D;D;D;D;D;D;.
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
.;.;.;.;.;.;.;D;D;D
Vest4
MutPred
Loss of stability (P = 0.0102);Loss of stability (P = 0.0102);Loss of stability (P = 0.0102);Loss of stability (P = 0.0102);Loss of stability (P = 0.0102);Loss of stability (P = 0.0102);Loss of stability (P = 0.0102);Loss of stability (P = 0.0102);Loss of stability (P = 0.0102);Loss of stability (P = 0.0102);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at