6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATA

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATA

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-29_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 67,642 control chromosomes in the GnomAD database, including 53 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 0.022 (47 hom., cov: 0)
  • Exomes 𝑓: 0.028 (6 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 (AMR) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-29_1433-14del		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-29_1433-14del		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 1020 AN: 46908 Hom.: 47 Cov.: 0

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.00140

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.00483

Gnomad FIN AF: 0.0228

Gnomad MID AF: 0.0179

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0176

GnomAD4 exome AF: 0.0284 AC: 588 AN: 20734 Hom.: 6 AF XY: 0.0274 AC XY: 322 AN XY: 11756

Gnomad4 AFR exome AF: 0.0242

Gnomad4 AMR exome AF: 0.0836

Gnomad4 ASJ exome AF: 0.0227

Gnomad4 EAS exome AF: 0.00667

Gnomad4 SAS exome AF: 0.00859

Gnomad4 FIN exome AF: 0.0291

Gnomad4 NFE exome AF: 0.0300

Gnomad4 OTH exome AF: 0.0348

GnomAD4 genome AF: 0.0218 AC: 1021 AN: 46908 Hom.: 47 Cov.: 0 AF XY: 0.0217 AC XY: 468 AN XY: 21548

Gnomad4 AFR AF: 0.0436

Gnomad4 AMR AF: 0.00857

Gnomad4 ASJ AF: 0.00140

Gnomad4 EAS AF: 0.0105

Gnomad4 SAS AF: 0.00483

Gnomad4 FIN AF: 0.0228

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.0175

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;