chr6-116732074-T-TTATATATA

Position:

• chr6-116732074-T-TTATATATA

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-21_1433-14dupTATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 67,188 control chromosomes in the GnomAD database, including 58 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 0.018 (58 hom., cov: 12)
  • Exomes 𝑓: 0.0011 (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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0182 (846/46368) while in subpopulation NFE AF= 0.0271 (576/21216). AF 95% confidence interval is 0.0253. There are 58 homozygotes in gnomad4. There are 334 alleles in male gnomad4 subpopulation. Median coverage is 12. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPNA5	NM_001366306.2	c.1433-21_1433-14dupTATATATA		intron_variant		ENST00000368564.7	NP_001353235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-21_1433-14dupTATATATA		intron_variant		1	NM_001366306.2	ENSP00000357552.1

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 847 AN: 46368 Hom.: 58 Cov.: 12

Gnomad AFR AF: 0.00962

Gnomad AMI AF: 0.00746

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.00909

Gnomad FIN AF: 0.00576

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0178

GnomAD4 exome AF: 0.00110 AC: 23 AN: 20820 Hom.: 0 AF XY: 0.000932 AC XY: 11 AN XY: 11802

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000952

Gnomad4 SAS exome AF: 0.000613

Gnomad4 FIN exome AF: 0.00419

Gnomad4 NFE exome AF: 0.000460

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0182 AC: 846 AN: 46368 Hom.: 58 Cov.: 12 AF XY: 0.0157 AC XY: 334 AN XY: 21310

Gnomad4 AFR AF: 0.00961

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.0115

Gnomad4 SAS AF: 0.00909

Gnomad4 FIN AF: 0.00576

Gnomad4 NFE AF: 0.0271

Gnomad4 OTH AF: 0.0177

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;