6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATA

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATA

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-43_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 67,666 control chromosomes in the GnomAD database, including 142 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 0.014 (46 hom., cov: 0)
  • Exomes 𝑓: 0.024 (96 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 (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPNA5	NM_001366306.2	c.1433-43_1433-14del		intron_variant		ENST00000368564.7	NP_001353235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-43_1433-14del		intron_variant		1	NM_001366306.2	ENSP00000357552	P4

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 643 AN: 46916 Hom.: 46 Cov.: 0

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00729

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00277

Gnomad SAS AF: 0.00138

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000697

Gnomad OTH AF: 0.00958

GnomAD4 exome AF: 0.0244 AC: 506 AN: 20752 Hom.: 96 AF XY: 0.0202 AC XY: 238 AN XY: 11770

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.0319

Gnomad4 ASJ exome AF: 0.00307

Gnomad4 EAS exome AF: 0.0238

Gnomad4 SAS exome AF: 0.0191

Gnomad4 FIN exome AF: 0.000836

Gnomad4 NFE exome AF: 0.0181

Gnomad4 OTH exome AF: 0.0450

GnomAD4 genome AF: 0.0137 AC: 641 AN: 46914 Hom.: 46 Cov.: 0 AF XY: 0.0131 AC XY: 283 AN XY: 21552

Gnomad4 AFR AF: 0.0399

Gnomad4 AMR AF: 0.00729

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00280

Gnomad4 SAS AF: 0.00138

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000697

Gnomad4 OTH AF: 0.00955

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;