chr19-45345791-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_177417.3(KLC3):c.250G>A(p.Glu84Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,548,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
KLC3
NM_177417.3 missense
NM_177417.3 missense
Scores
5
6
3
Clinical Significance
Conservation
PhyloP100: 9.72
Genes affected
KLC3 (HGNC:20717): (kinesin light chain 3) This gene encodes a member of the kinesin light chain gene family. Kinesins are molecular motors involved in the transport of cargo along microtubules, and are composed of two kinesin heavy chain (KHC) and two kinesin light chain (KLC) molecules. KLCs are thought to typically be involved in binding cargo and regulating kinesin activity. In the rat, a protein similar to this gene product is expressed in post-meiotic spermatids, where it associates with structural components of sperm tails and mitochondria. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLC3 | NM_177417.3 | c.250G>A | p.Glu84Lys | missense_variant | 2/13 | ENST00000391946.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLC3 | ENST00000391946.7 | c.250G>A | p.Glu84Lys | missense_variant | 2/13 | 1 | NM_177417.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152050Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000275 AC: 4AN: 145278Hom.: 0 AF XY: 0.0000386 AC XY: 3AN XY: 77622
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GnomAD4 exome AF: 0.0000122 AC: 17AN: 1396318Hom.: 0 Cov.: 32 AF XY: 0.0000145 AC XY: 10AN XY: 688600
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152050Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74270
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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 | Mar 04, 2024 | The c.250G>A (p.E84K) alteration is located in exon 2 (coding exon 1) of the KLC3 gene. This alteration results from a G to A substitution at nucleotide position 250, causing the glutamic acid (E) at amino acid position 84 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
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
T
Sift4G
Uncertain
D;D;D;D;D
Polyphen
0.99, 0.98
.;D;D;.;D
Vest4
0.81, 0.88, 0.79
MutPred
Gain of ubiquitination at E84 (P = 0.0192);Gain of ubiquitination at E84 (P = 0.0192);Gain of ubiquitination at E84 (P = 0.0192);Gain of ubiquitination at E84 (P = 0.0192);.;
MVP
MPC
0.089
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