6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATATATA

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATATATA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001366306.2(KPNA5):​c.1433-23_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 67,632 control chromosomes in the GnomAD database, including 24 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 0.019 (24 hom., cov: 0)
  • Exomes 𝑓: 0.0048 (0 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.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0186 (871/46840) while in subpopulation SAS AF= 0.0348 (50/1438). AF 95% confidence interval is 0.0271. There are 24 homozygotes in gnomad4. There are 423 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-23_1433-14del		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-23_1433-14del		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 868 AN: 46840 Hom.: 24 Cov.: 0

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0284

Gnomad ASJ AF: 0.00772

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.00664

Gnomad MID AF: 0.0357

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0288

GnomAD4 exome AF: 0.00481 AC: 100 AN: 20792 Hom.: 0 AF XY: 0.00492 AC XY: 58 AN XY: 11794

Gnomad4 AFR exome AF: 0.00313

Gnomad4 AMR exome AF: 0.00694

Gnomad4 ASJ exome AF: 0.00307

Gnomad4 EAS exome AF: 0.00865

Gnomad4 SAS exome AF: 0.00429

Gnomad4 FIN exome AF: 0.00307

Gnomad4 NFE exome AF: 0.00544

Gnomad4 OTH exome AF: 0.00307

GnomAD4 genome AF: 0.0186 AC: 871 AN: 46840 Hom.: 24 Cov.: 0 AF XY: 0.0197 AC XY: 423 AN XY: 21516

Gnomad4 AFR AF: 0.0194

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.00772

Gnomad4 EAS AF: 0.0105

Gnomad4 SAS AF: 0.0348

Gnomad4 FIN AF: 0.00664

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.0287

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;