6-116732074-TTATATATATATATATATATATATATATATATA-T

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATA-T

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-45_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 67,702 control chromosomes in the GnomAD database, including 34 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 0.00032 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0076 (34 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 GnomAdExome4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-45_1433-14del		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-45_1433-14del		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.000320 AC: 15 AN: 46916 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000344

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000692

Gnomad SAS AF: 0.000691

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000371

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00760 AC: 158 AN: 20786 Hom.: 34 AF XY: 0.00696 AC XY: 82 AN XY: 11790

Gnomad4 AFR exome AF: 0.0202

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00191

Gnomad4 SAS exome AF: 0.00306

Gnomad4 FIN exome AF: 0.00279

Gnomad4 NFE exome AF: 0.0100

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.000320 AC: 15 AN: 46916 Hom.: 0 Cov.: 0 AF XY: 0.000371 AC XY: 8 AN XY: 21554

Gnomad4 AFR AF: 0.000344

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000699

Gnomad4 SAS AF: 0.000691

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000371

Gnomad4 OTH AF: 0.00

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;