5-170732837-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_014592.4(KCNIP1):c.473T>C(p.Met158Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,016 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 0.0000066 ( 0 hom., cov: 31)
Consequence
KCNIP1
NM_014592.4 missense
NM_014592.4 missense
Scores
10
6
1
Clinical Significance
Conservation
PhyloP100: 8.02
Genes affected
KCNIP1 (HGNC:15521): (potassium voltage-gated channel interacting protein 1) This gene encodes a member of the family of cytosolic voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the neuronal calcium sensor (NCS) family of the calcium binding EF-hand proteins. They associate with Kv4 alpha subunits to form native Kv4 channel complexes. The encoded protein may regulate rapidly inactivating (A-type) currents, and hence neuronal membrane excitability, in response to changes in the concentration of intracellular calcium. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.853
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNIP1 | NM_014592.4 | c.473T>C | p.Met158Thr | missense_variant | 6/8 | ENST00000328939.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNIP1 | ENST00000328939.9 | c.473T>C | p.Met158Thr | missense_variant | 6/8 | 1 | NM_014592.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152016Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD4 exome Cov.: 29
GnomAD4 exome
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29
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152016Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74262
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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 | Jan 26, 2022 | The c.506T>C (p.M169T) alteration is located in exon 7 (coding exon 7) of the KCNIP1 gene. This alteration results from a T to C substitution at nucleotide position 506, causing the methionine (M) at amino acid position 169 to be replaced by a threonine (T). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D;D;D;D;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;D;D;D;D;.;.
Sift4G
Uncertain
D;D;D;D;D;T;.;D
Polyphen
0.98
.;.;.;.;.;D;.;.
Vest4
MutPred
0.59
.;.;.;.;.;Loss of stability (P = 0.0386);.;.;
MVP
MPC
1.7
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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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