6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATA

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATA

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-37_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0052 in 67,726 control chromosomes in the GnomAD database, including 19 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 0.0025 (5 hom., cov: 0)
  • Exomes 𝑓: 0.011 (14 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 eas. gnomad4_exome allele frequency = 0.0112 (233/20812) while in subpopulation EAS AF= 0.0421 (44/1046). AF 95% confidence interval is 0.0322. There are 14 homozygotes in gnomad4_exome. There are 119 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-37_1433-14del		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-37_1433-14del		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 118 AN: 46914 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.00282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00407

Gnomad ASJ AF: 0.000701

Gnomad EAS AF: 0.00692

Gnomad SAS AF: 0.00829

Gnomad FIN AF: 0.000951

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00153

Gnomad OTH AF: 0.00160

GnomAD4 exome AF: 0.0112 AC: 233 AN: 20812 Hom.: 14 AF XY: 0.0101 AC XY: 119 AN XY: 11802

Gnomad4 AFR exome AF: 0.0105

Gnomad4 AMR exome AF: 0.0152

Gnomad4 ASJ exome AF: 0.0123

Gnomad4 EAS exome AF: 0.0421

Gnomad4 SAS exome AF: 0.0172

Gnomad4 FIN exome AF: 0.000836

Gnomad4 NFE exome AF: 0.00994

Gnomad4 OTH exome AF: 0.0153

GnomAD4 genome AF: 0.00254 AC: 119 AN: 46914 Hom.: 5 Cov.: 0 AF XY: 0.00334 AC XY: 72 AN XY: 21552

Gnomad4 AFR AF: 0.00289

Gnomad4 AMR AF: 0.00407

Gnomad4 ASJ AF: 0.000701

Gnomad4 EAS AF: 0.00699

Gnomad4 SAS AF: 0.00829

Gnomad4 FIN AF: 0.000951

Gnomad4 NFE AF: 0.00153

Gnomad4 OTH AF: 0.00159

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;