6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATA

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATA

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-31_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 67,636 control chromosomes in the GnomAD database, including 176 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 0.044 (125 hom., cov: 0)
  • Exomes 𝑓: 0.062 (51 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: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-31_1433-14del		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-31_1433-14del		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 2042 AN: 46920 Hom.: 124 Cov.: 0

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.0214

Gnomad AMR AF: 0.0364

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0242

Gnomad SAS AF: 0.0200

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0357

Gnomad NFE AF: 0.0425

Gnomad OTH AF: 0.0463

GnomAD4 exome AF: 0.0623 AC: 1290 AN: 20714 Hom.: 51 AF XY: 0.0614 AC XY: 723 AN XY: 11768

Gnomad4 AFR exome AF: 0.0303

Gnomad4 AMR exome AF: 0.0306

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.0269

Gnomad4 SAS exome AF: 0.0153

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.0616

Gnomad4 OTH exome AF: 0.0368

GnomAD4 genome AF: 0.0436 AC: 2048 AN: 46922 Hom.: 125 Cov.: 0 AF XY: 0.0422 AC XY: 910 AN XY: 21554

Gnomad4 AFR AF: 0.0372

Gnomad4 AMR AF: 0.0364

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0244

Gnomad4 SAS AF: 0.0200

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.0425

Gnomad4 OTH AF: 0.0492

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;