chr6-116732074-TTATATATATATATATATATATATATATATATATATATA-T

Position:

• chr6-116732074-TTATATATATATATATATATATATATATATATATATATA-T

Variant summary

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

The NM_001366306.2(KPNA5):​c.1433-51_1433-14delTATATATATATATATATATATATATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 67,758 control chromosomes in the GnomAD database, including 7 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 0.000043 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00086 (7 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 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPNA5	NM_001366306.2	c.1433-51_1433-14delTATATATATATATATATATATATATATATATATATATA		intron_variant		ENST00000368564.7	NP_001353235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPNA5	ENST00000368564.7	c.1433-61_1433-24delTATATATATATATATATATATATATATATATATATATA		intron_variant		1	NM_001366306.2	ENSP00000357552.1

Frequencies

GnomAD3 genomes AF: 0.0000426 AC: 2 AN: 46916 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000864 AC: 18 AN: 20842 Hom.: 7 AF XY: 0.00127 AC XY: 15 AN XY: 11818

Gnomad4 AFR exome AF: 0.00209

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00190

Gnomad4 SAS exome AF: 0.00490

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000552

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000426 AC: 2 AN: 46916 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 21550

Gnomad4 AFR AF: 0.000138

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

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;