chr13-49702390-T-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_002267.4(KPNA3):c.1463A>C(p.Asp488Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,430,780 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 (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
KPNA3
NM_002267.4 missense
NM_002267.4 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 7.97
Genes affected
KPNA3 (HGNC:6396): (karyopherin subunit alpha 3) The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC), which consists of 60-100 proteins. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion while larger molecules are transported by an active process. The protein encoded by this gene belongs to the importin alpha family, and is involved in nuclear protein import. [provided by RefSeq, Jan 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, KPNA3
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2488432).
BS2
?
High AC in GnomAd at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KPNA3 | NM_002267.4 | c.1463A>C | p.Asp488Ala | missense_variant | 16/17 | ENST00000261667.8 | |
KPNA3 | XM_017020561.2 | c.1391A>C | p.Asp464Ala | missense_variant | 16/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KPNA3 | ENST00000261667.8 | c.1463A>C | p.Asp488Ala | missense_variant | 16/17 | 1 | NM_002267.4 | P1 | |
KPNA3 | ENST00000436760.1 | c.224A>C | p.Asp75Ala | missense_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152230Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000117 AC: 28AN: 238644Hom.: 0 AF XY: 0.000147 AC XY: 19AN XY: 129210
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GnomAD4 exome AF: 0.000167 AC: 214AN: 1278550Hom.: 0 Cov.: 19 AF XY: 0.000166 AC XY: 107AN XY: 644636
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2024 | The c.1463A>C (p.D488A) alteration is located in exon 16 (coding exon 16) of the KPNA3 gene. This alteration results from a A to C substitution at nucleotide position 1463, causing the aspartic acid (D) at amino acid position 488 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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