6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATATATATATATATATATATATATATATA

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATATATATATATATATATATATATATATA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001366306.2(KPNA5):​c.1433-25_1433-14dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 67,472 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 0.0081 (24 hom., cov: 12)
  • Exomes 𝑓: 0.000096 (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 Likely_benign. Variant got -4 ACMG points.

• 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.1433-25_1433-14dup		intron_variant		ENST00000368564.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00808 AC: 377 AN: 46648 Hom.: 24 Cov.: 12

Gnomad AFR AF: 0.00470

Gnomad AMI AF: 0.00714

Gnomad AMR AF: 0.00495

Gnomad ASJ AF: 0.00708

Gnomad EAS AF: 0.00279

Gnomad SAS AF: 0.00349

Gnomad FIN AF: 0.000951

Gnomad MID AF: 0.0185

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.00968

GnomAD4 exome AF: 0.0000960 AC: 2 AN: 20824 Hom.: 0 AF XY: 0.000169 AC XY: 2 AN XY: 11804

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000184

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00808 AC: 377 AN: 46648 Hom.: 24 Cov.: 12 AF XY: 0.00798 AC XY: 171 AN XY: 21440

Gnomad4 AFR AF: 0.00470

Gnomad4 AMR AF: 0.00495

Gnomad4 ASJ AF: 0.00708

Gnomad4 EAS AF: 0.00282

Gnomad4 SAS AF: 0.00349

Gnomad4 FIN AF: 0.000951

Gnomad4 NFE AF: 0.0121

Gnomad4 OTH AF: 0.00965

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;