Genetic Variant KPNA5:c.1433-31_1433-14delTATATATATATATATATA (chr6-116732074-TTATATATATATATATATA-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.1433-31_1433-14delTATATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 67,636 control chromosomes in the GnomAD database, including 176 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 0.044 ( 125 hom., cov: 0)

Exomes 𝑓: 0.062 ( 51 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:

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ACMG classification

Classification was made for transcript

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

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA5	NM_001366306.2 link	c.1433-31_1433-14delTATATATATATATATATA		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_1433-44delTATATATATATATATATA		intron_variant	Intron 13 of 13	1	NM_001366306.2	ENSP00000357552.1		O15131

Frequencies

GnomAD3 genomes

AF:

0.0435

AC:

2042

AN:

46920

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0370

Gnomad AMI

AF:

0.0214

Gnomad AMR

AF:

0.0364

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.0242

Gnomad SAS

AF:

0.0200

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.0357

Gnomad NFE

AF:

0.0425

Gnomad OTH

AF:

0.0463

GnomAD4 exome

AF:

0.0623

AC:

1290

AN:

20714

Hom.:

AF XY:

0.0614

AC XY:

723

AN XY:

11768

show subpopulations

African (AFR)

AF:

0.0303

AC:

AN:

956

American (AMR)

AF:

0.0306

AC:

AN:

718

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

101

AN:

974

East Asian (EAS)

AF:

0.0269

AC:

AN:

1042

South Asian (SAS)

AF:

0.0153

AC:

AN:

1632

European-Finnish (FIN)

AF:

0.107

AC:

380

AN:

3540

Middle Eastern (MID)

AF:

0.0469

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0616

AC:

666

AN:

10810

Other (OTH)

AF:

0.0368

AC:

AN:

978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

115

154

192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0436

AC:

2048

AN:

46922

Hom.:

125

Cov.:

AF XY:

0.0422

AC XY:

910

AN XY:

21554

show subpopulations

African (AFR)

AF:

0.0372

AC:

541

AN:

14526

American (AMR)

AF:

0.0364

AC:

170

AN:

4666

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

155

AN:

1426

East Asian (EAS)

AF:

0.0244

AC:

AN:

1432

South Asian (SAS)

AF:

0.0200

AC:

AN:

1448

European-Finnish (FIN)

AF:

0.157

AC:

166

AN:

1056

Middle Eastern (MID)

AF:

0.0385

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0425

AC:

916

AN:

21546

Other (OTH)

AF:

0.0492

AC:

AN:

630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.547

Heterozygous variant carriers

103

155

206

258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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

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6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATATATATATATATA

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