6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATATATATATATATATATATATA

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATATATATATATATATATATATA

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-19_1433-14dup 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 67,242 control chromosomes in the GnomAD database, including 89 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 0.021 (89 hom., cov: 12)
  • Exomes 𝑓: 0.00072 (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 nfe. gnomad4 allele frequency = 0.0205 (952/46434) while in subpopulation NFE AF= 0.0293 (622/21260). AF 95% confidence interval is 0.0274. There are 89 homozygotes in gnomad4. There are 434 alleles in male gnomad4 subpopulation. Median coverage is 12. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 89 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-19_1433-14dup		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-19_1433-14dup		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 952 AN: 46432 Hom.: 89 Cov.: 12

Gnomad AFR AF: 0.00886

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.0234

Gnomad SAS AF: 0.0146

Gnomad FIN AF: 0.00668

Gnomad MID AF: 0.0179

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0194

GnomAD4 exome AF: 0.000721 AC: 15 AN: 20808 Hom.: 0 AF XY: 0.00102 AC XY: 12 AN XY: 11796

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000613

Gnomad4 FIN exome AF: 0.00195

Gnomad4 NFE exome AF: 0.000645

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0205 AC: 952 AN: 46434 Hom.: 89 Cov.: 12 AF XY: 0.0203 AC XY: 434 AN XY: 21328

Gnomad4 AFR AF: 0.00885

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.0363

Gnomad4 EAS AF: 0.0237

Gnomad4 SAS AF: 0.0146

Gnomad4 FIN AF: 0.00668

Gnomad4 NFE AF: 0.0293

Gnomad4 OTH AF: 0.0193

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;