6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATATATATATATATA

Variant names:

• chr6-116732074-TTA-T
• rs2243369
• NM_001366306.2:c.1433-15_1433-14delTA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001366306.2(KPNA5):​c.1433-15_1433-14delTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 67,668 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 0.0053 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0014 (0 hom.)
• Consequence: KPNA5 NM_001366306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366306.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPNA5	NM_001366306.2	MANE Select	c.1433-15_1433-14delTA		intron	N/A	NP_001353235.1	O15131
	KPNA5	NM_001366304.1		c.1493-15_1493-14delTA		intron	N/A	NP_001353233.1	A0A8V8TMV2
	KPNA5	NM_001366305.2		c.1493-15_1493-14delTA		intron	N/A	NP_001353234.1	A0A8V8TMV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPNA5	ENST00000368564.7	TSL:1 MANE Select	c.1433-61_1433-60delTA		intron	N/A	ENSP00000357552.1	O15131
	KPNA5	ENST00000356348.6	TSL:1	c.1433-61_1433-60delTA		intron	N/A	ENSP00000348704.1	O15131
	KPNA5	ENST00000937498.1		c.1508-61_1508-60delTA		intron	N/A	ENSP00000607557.1

Frequencies

GnomAD3 genomes AF: 0.00523 AC: 245 AN: 46850 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00644

Gnomad ASJ AF: 0.00562

Gnomad EAS AF: 0.00556

Gnomad SAS AF: 0.00138

Gnomad FIN AF: 0.00862

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00716

Gnomad OTH AF: 0.00319

GnomAD4 exome AF: 0.00139 AC: 29 AN: 20818 Hom.: 0 AF XY: 0.00119 AC XY: 14 AN XY: 11810

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 958

American (AMR) AF: 0.00139 AC: 1 AN: 722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 972

East Asian (EAS) AF: 0.00 AC: 0 AN: 1046

South Asian (SAS) AF: 0.00 AC: 0 AN: 1630

European-Finnish (FIN) AF: 0.00195 AC: 7 AN: 3586

Middle Eastern (MID) AF: 0.0156 AC: 1 AN: 64

European-Non Finnish (NFE) AF: 0.00175 AC: 19 AN: 10858

Other (OTH) AF: 0.00102 AC: 1 AN: 982

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00525 AC: 246 AN: 46850 Hom.: 1 Cov.: 0 AF XY: 0.00497 AC XY: 107 AN XY: 21508

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00227 AC: 33 AN: 14524

American (AMR) AF: 0.00645 AC: 30 AN: 4654

Ashkenazi Jewish (ASJ) AF: 0.00562 AC: 8 AN: 1424

East Asian (EAS) AF: 0.00562 AC: 8 AN: 1424

South Asian (SAS) AF: 0.00138 AC: 2 AN: 1448

European-Finnish (FIN) AF: 0.00862 AC: 9 AN: 1044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 52

European-Non Finnish (NFE) AF: 0.00716 AC: 154 AN: 21512

Other (OTH) AF: 0.00318 AC: 2 AN: 628

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2243369;

hg19: chr6-117053237;