Genetic Variant KPNA5:c.1433-27_1433-14delTATATATATATATA (chr6-116732074-TTATATATATATATA-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001366306.2(KPNA5):c.1433-27_1433-14delTATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0695 in 67,464 control chromosomes in the GnomAD database, including 258 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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 0.083 ( 244 hom., cov: 0)

Exomes 𝑓: 0.040 ( 14 hom. )

Consequence

KPNA5
NM_001366306.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

3 publications found

Variant links:

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]

KPNA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA5	NM_001366306.2 link	c.1433-27_1433-14delTATATATATATATA		intron_variant	Intron 13 of 13	ENST00000368564.7	NP_001353235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KPNA5	ENST00000368564.7 link	c.1433-61_1433-48delTATATATATATATA		intron_variant	Intron 13 of 13	1	NM_001366306.2	ENSP00000357552.1		O15131

Frequencies

GnomAD3 genomes

AF:

0.0827

AC:

3871

AN:

46794

Hom.:

243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0629

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.0767

Gnomad EAS

AF:

0.0367

Gnomad SAS

AF:

0.0311

Gnomad FIN

AF:

0.0627

Gnomad MID

AF:

0.0357

Gnomad NFE

AF:

0.0715

Gnomad OTH

AF:

0.0946

GnomAD4 exome

AF:

0.0397

AC:

821

AN:

20670

Hom.:

AF XY:

0.0412

AC XY:

483

AN XY:

11726

show subpopulations

African (AFR)

AF:

0.0221

AC:

AN:

952

American (AMR)

AF:

0.154

AC:

109

AN:

708

Ashkenazi Jewish (ASJ)

AF:

0.0351

AC:

AN:

970

East Asian (EAS)

AF:

0.0162

AC:

AN:

1048

South Asian (SAS)

AF:

0.0111

AC:

AN:

1628

European-Finnish (FIN)

AF:

0.0382

AC:

136

AN:

3560

Middle Eastern (MID)

AF:

0.0323

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0406

AC:

437

AN:

10772

Other (OTH)

AF:

0.0485

AC:

AN:

970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.404

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0827

AC:

3870

AN:

46794

Hom.:

244

Cov.:

AF XY:

0.0827

AC XY:

1776

AN XY:

21488

show subpopulations

African (AFR)

AF:

0.0627

AC:

909

AN:

14496

American (AMR)

AF:

0.235

AC:

1087

AN:

4628

Ashkenazi Jewish (ASJ)

AF:

0.0767

AC:

109

AN:

1422

East Asian (EAS)

AF:

0.0371

AC:

AN:

1428

South Asian (SAS)

AF:

0.0318

AC:

AN:

1448

European-Finnish (FIN)

AF:

0.0627

AC:

AN:

1052

Middle Eastern (MID)

AF:

0.0385

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0715

AC:

1537

AN:

21502

Other (OTH)

AF:

0.0942

AC:

AN:

626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

196

293

391

489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

BranchPoint Hunter

2.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATATATA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over