6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATATA

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATATA

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-25_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 67,604 control chromosomes in the GnomAD database, including 41 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 0.025 (39 hom., cov: 0)
  • Exomes 𝑓: 0.012 (2 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 = 0.0246 (1154/46852) while in subpopulation SAS AF= 0.0589 (85/1442). AF 95% confidence interval is 0.0488. There are 39 homozygotes in gnomad4. There are 535 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-25_1433-14del		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-25_1433-14del		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 1153 AN: 46852 Hom.: 39 Cov.: 0

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.00714

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0310

Gnomad EAS AF: 0.00830

Gnomad SAS AF: 0.0589

Gnomad FIN AF: 0.0247

Gnomad MID AF: 0.0179

Gnomad NFE AF: 0.0260

Gnomad OTH AF: 0.0208

GnomAD4 exome AF: 0.0117 AC: 243 AN: 20752 Hom.: 2 AF XY: 0.0125 AC XY: 147 AN XY: 11764

Gnomad4 AFR exome AF: 0.00523

Gnomad4 AMR exome AF: 0.0252

Gnomad4 ASJ exome AF: 0.00821

Gnomad4 EAS exome AF: 0.00575

Gnomad4 SAS exome AF: 0.0123

Gnomad4 FIN exome AF: 0.0109

Gnomad4 NFE exome AF: 0.0119

Gnomad4 OTH exome AF: 0.0174

GnomAD4 genome AF: 0.0246 AC: 1154 AN: 46852 Hom.: 39 Cov.: 0 AF XY: 0.0248 AC XY: 535 AN XY: 21530

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0310

Gnomad4 EAS AF: 0.00839

Gnomad4 SAS AF: 0.0589

Gnomad4 FIN AF: 0.0247

Gnomad4 NFE AF: 0.0261

Gnomad4 OTH AF: 0.0208

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;