6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATA

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATA

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-27_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0695 in 67,464 control chromosomes in the GnomAD database, including 258 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 0.083 (244 hom., cov: 0)
  • Exomes 𝑓: 0.040 (14 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 (AMR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-27_1433-14del		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-27_1433-14del		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 3871 AN: 46794 Hom.: 243 Cov.: 0

Gnomad AFR AF: 0.0629

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.0367

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.0627

Gnomad MID AF: 0.0357

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0946

GnomAD4 exome AF: 0.0397 AC: 821 AN: 20670 Hom.: 14 AF XY: 0.0412 AC XY: 483 AN XY: 11726

Gnomad4 AFR exome AF: 0.0221

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.0351

Gnomad4 EAS exome AF: 0.0162

Gnomad4 SAS exome AF: 0.0111

Gnomad4 FIN exome AF: 0.0382

Gnomad4 NFE exome AF: 0.0406

Gnomad4 OTH exome AF: 0.0485

GnomAD4 genome AF: 0.0827 AC: 3870 AN: 46794 Hom.: 244 Cov.: 0 AF XY: 0.0827 AC XY: 1776 AN XY: 21488

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.0767

Gnomad4 EAS AF: 0.0371

Gnomad4 SAS AF: 0.0318

Gnomad4 FIN AF: 0.0627

Gnomad4 NFE AF: 0.0715

Gnomad4 OTH AF: 0.0942

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;