6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATA

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATA

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-35_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 67,716 control chromosomes in the GnomAD database, including 88 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 0.012 (47 hom., cov: 0)
  • Exomes 𝑓: 0.031 (41 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 = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-35_1433-14del		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-35_1433-14del		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 585 AN: 46920 Hom.: 47 Cov.: 0

Gnomad AFR AF: 0.00682

Gnomad AMI AF: 0.0357

Gnomad AMR AF: 0.00922

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.0138

Gnomad FIN AF: 0.0228

Gnomad MID AF: 0.0714

Gnomad NFE AF: 0.00822

Gnomad OTH AF: 0.0128

GnomAD4 exome AF: 0.0308 AC: 641 AN: 20796 Hom.: 41 AF XY: 0.0305 AC XY: 360 AN XY: 11790

Gnomad4 AFR exome AF: 0.00837

Gnomad4 AMR exome AF: 0.0125

Gnomad4 ASJ exome AF: 0.0400

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.0172

Gnomad4 FIN exome AF: 0.0204

Gnomad4 NFE exome AF: 0.0282

Gnomad4 OTH exome AF: 0.0297

GnomAD4 genome AF: 0.0124 AC: 581 AN: 46920 Hom.: 47 Cov.: 0 AF XY: 0.0132 AC XY: 285 AN XY: 21556

Gnomad4 AFR AF: 0.00667

Gnomad4 AMR AF: 0.00922

Gnomad4 ASJ AF: 0.0182

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.0131

Gnomad4 FIN AF: 0.0228

Gnomad4 NFE AF: 0.00822

Gnomad4 OTH AF: 0.0127

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;