6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATA

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001366306.2(KPNA5):​c.1433-33_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 67,686 control chromosomes in the GnomAD database, including 128 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.018 (61 hom., cov: 0)
  • Exomes 𝑓: 0.044 (67 hom.)
• Consequence: KPNA5 NM_001366306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

Genes affected

KPNA5 (HGNC:6398): (karyopherin subunit alpha 5) 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 and is probably 120 million daltons in molecular size. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion; larger molecules are transported by an active process. Most nuclear proteins contain short basic amino acid sequences known as nuclear localization signals (NLSs). KPNA5 protein belongs to the importin alpha protein family and is thought to be involved in NLS-dependent protein import into the nucleus. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-33_1433-14del		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-33_1433-14del		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 859 AN: 46910 Hom.: 61 Cov.: 0

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.00982

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.00691

Gnomad FIN AF: 0.00951

Gnomad MID AF: 0.0179

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0112

GnomAD4 exome AF: 0.0437 AC: 908 AN: 20776 Hom.: 67 AF XY: 0.0408 AC XY: 481 AN XY: 11780

Gnomad4 AFR exome AF: 0.0136

Gnomad4 AMR exome AF: 0.0182

Gnomad4 ASJ exome AF: 0.0512

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.0154

Gnomad4 FIN exome AF: 0.0292

Gnomad4 NFE exome AF: 0.0477

Gnomad4 OTH exome AF: 0.0459

GnomAD4 genome AF: 0.0182 AC: 855 AN: 46910 Hom.: 61 Cov.: 0 AF XY: 0.0187 AC XY: 403 AN XY: 21552

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.00858

Gnomad4 ASJ AF: 0.00982

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.00691

Gnomad4 FIN AF: 0.00951

Gnomad4 NFE AF: 0.0175

Gnomad4 OTH AF: 0.0111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2243369; hg19: chr6-117053237;