rs757545358
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_007317.3(KIF22):āc.1387A>Gā(p.Thr463Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,611,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 30)
Exomes š: 0.000018 ( 0 hom. )
Consequence
KIF22
NM_007317.3 missense
NM_007317.3 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 4.93
Genes affected
KIF22 (HGNC:6391): (kinesin family member 22) The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. The C-terminal half of this protein has been shown to bind DNA. Studies with the Xenopus homolog suggests its essential role in metaphase chromosome alignment and maintenance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.26913255).
BS2
High AC in GnomAdExome4 at 26 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF22 | NM_007317.3 | c.1387A>G | p.Thr463Ala | missense_variant | 9/14 | ENST00000160827.9 | |
KIF22 | NM_001256269.2 | c.1183A>G | p.Thr395Ala | missense_variant | 10/15 | ||
KIF22 | NM_001256270.1 | c.1183A>G | p.Thr395Ala | missense_variant | 9/14 | ||
KIF22 | XM_047434094.1 | c.1387A>G | p.Thr463Ala | missense_variant | 9/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF22 | ENST00000160827.9 | c.1387A>G | p.Thr463Ala | missense_variant | 9/14 | 1 | NM_007317.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152038Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248908Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134590
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1459868Hom.: 0 Cov.: 29 AF XY: 0.0000165 AC XY: 12AN XY: 726208
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152038Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74240
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 04, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2023 | This variant has not been reported in the literature in individuals affected with KIF22-related conditions. This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 463 of the KIF22 protein (p.Thr463Ala). This variant is present in population databases (rs757545358, gnomAD 0.002%). ClinVar contains an entry for this variant (Variation ID: 520925). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KIF22 protein function. Experimental studies have shown that this missense change affects KIF22 function (PMID: 12727876). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Spondyloepimetaphyseal dysplasia with multiple dislocations Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | Aug 06, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;T;T
Polyphen
0.92
.;P;.;.
Vest4
MutPred
0.20
.;Loss of phosphorylation at T463 (P = 0.0075);.;.;
MVP
MPC
0.84
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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