chr6-116732074-TTATA-T

Position:

• chr6-116732074-TTATA-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366306.2(KPNA5):​c.1433-17_1433-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 67,680 control chromosomes in the GnomAD database, including 1 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 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00082 (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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA5	NM_001366306.2	c.1433-17_1433-14del		intron_variant		ENST00000368564.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-17_1433-14del		intron_variant		1	NM_001366306.2	P4

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 118 AN: 46878 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00277

Gnomad SAS AF: 0.00139

Gnomad FIN AF: 0.00190

Gnomad MID AF: 0.0179

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.00160

GnomAD4 exome AF: 0.000817 AC: 17 AN: 20802 Hom.: 0 AF XY: 0.000932 AC XY: 11 AN XY: 11806

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: 0.00

Gnomad4 FIN exome AF: 0.00112

Gnomad4 NFE exome AF: 0.000922

Gnomad4 OTH exome AF: 0.00102

GnomAD4 genome AF: 0.00252 AC: 118 AN: 46878 Hom.: 1 Cov.: 0 AF XY: 0.00246 AC XY: 53 AN XY: 21534

Gnomad4 AFR AF: 0.00186

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00280

Gnomad4 SAS AF: 0.00139

Gnomad4 FIN AF: 0.00190

Gnomad4 NFE AF: 0.00251

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

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;