chr6-116732074-TTATATATA-T

Position:

• chr6-116732074-TTATATATA-T

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-21_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00417 in 67,690 control chromosomes in the GnomAD database, including 3 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 0.0049 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0025 (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 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-21_1433-14del		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-21_1433-14del		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 232 AN: 46886 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00281

Gnomad EAS AF: 0.00830

Gnomad SAS AF: 0.00552

Gnomad FIN AF: 0.000949

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00348

Gnomad OTH AF: 0.00319

GnomAD4 exome AF: 0.00245 AC: 51 AN: 20804 Hom.: 0 AF XY: 0.00254 AC XY: 30 AN XY: 11792

Gnomad4 AFR exome AF: 0.00104

Gnomad4 AMR exome AF: 0.00278

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00478

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00391

Gnomad4 NFE exome AF: 0.00249

Gnomad4 OTH exome AF: 0.00204

GnomAD4 genome AF: 0.00493 AC: 231 AN: 46886 Hom.: 3 Cov.: 0 AF XY: 0.00539 AC XY: 116 AN XY: 21534

Gnomad4 AFR AF: 0.00778

Gnomad4 AMR AF: 0.00344

Gnomad4 ASJ AF: 0.00281

Gnomad4 EAS AF: 0.00839

Gnomad4 SAS AF: 0.00552

Gnomad4 FIN AF: 0.000949

Gnomad4 NFE AF: 0.00348

Gnomad4 OTH AF: 0.00318

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;