6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATATATATATATATATATA

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATATATATATATATATATA

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-15_1433-14dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 67,412 control chromosomes in the GnomAD database, including 48 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 (48 hom., cov: 12)
  • Exomes 𝑓: 0.00077 (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 = 0.0211 (983/46598) while in subpopulation NFE AF= 0.031 (664/21402). AF 95% confidence interval is 0.0291. There are 48 homozygotes in gnomad4. There are 417 alleles in male gnomad4 subpopulation. Median coverage is 12. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-15_1433-14dup		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-15_1433-14dup		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 983 AN: 46600 Hom.: 48 Cov.: 12

Gnomad AFR AF: 0.00810

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0318

Gnomad EAS AF: 0.0176

Gnomad SAS AF: 0.00484

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0310

Gnomad OTH AF: 0.0225

GnomAD4 exome AF: 0.000769 AC: 16 AN: 20814 Hom.: 0 AF XY: 0.000762 AC XY: 9 AN XY: 11804

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000952

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00140

Gnomad4 NFE exome AF: 0.000645

Gnomad4 OTH exome AF: 0.00102

GnomAD4 genome AF: 0.0211 AC: 983 AN: 46598 Hom.: 48 Cov.: 12 AF XY: 0.0195 AC XY: 417 AN XY: 21416

Gnomad4 AFR AF: 0.00809

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.0318

Gnomad4 EAS AF: 0.0178

Gnomad4 SAS AF: 0.00484

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.0310

Gnomad4 OTH AF: 0.0224

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;