6-116732074-TTATATATATATATATATATATATATA-T

Position:

• chr6-116732074-TTATATATATATATATATATATATATA-T

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-39_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 67,720 control chromosomes in the GnomAD database, including 278 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 0.052 (154 hom., cov: 0)
  • Exomes 𝑓: 0.056 (124 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 (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-39_1433-14del		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-39_1433-14del		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.0518 AC: 2430 AN: 46920 Hom.: 155 Cov.: 0

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0414

Gnomad EAS AF: 0.00553

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0893

Gnomad NFE AF: 0.00311

Gnomad OTH AF: 0.0463

GnomAD4 exome AF: 0.0563 AC: 1172 AN: 20800 Hom.: 124 AF XY: 0.0605 AC XY: 714 AN XY: 11796

Gnomad4 AFR exome AF: 0.247

Gnomad4 AMR exome AF: 0.0333

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.0154

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.00111

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.0517 AC: 2427 AN: 46920 Hom.: 154 Cov.: 0 AF XY: 0.0562 AC XY: 1212 AN XY: 21550

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.0414

Gnomad4 EAS AF: 0.00490

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00311

Gnomad4 OTH AF: 0.0446

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;