Genetic Variant KPNA5:c.1433-39_1433-14delTATATATATATATATATATATATATA (chr6-116732074-TTATATATATATATATATATATATATA-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.1433-39_1433-14delTATATATATATATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 67,720 control chromosomes in the GnomAD database, including 278 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 0.052 ( 154 hom., cov: 0)

Exomes 𝑓: 0.056 ( 124 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

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA5	NM_001366306.2 link	c.1433-39_1433-14delTATATATATATATATATATATATATA		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_1433-36delTATATATATATATATATATATATATA		intron_variant	Intron 13 of 13	1	NM_001366306.2	ENSP00000357552.1		O15131

Frequencies

GnomAD3 genomes

AF:

0.0518

AC:

2430

AN:

46920

Hom.:

155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.0414

Gnomad EAS

AF:

0.00553

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0893

Gnomad NFE

AF:

0.00311

Gnomad OTH

AF:

0.0463

GnomAD4 exome

AF:

0.0563

AC:

1172

AN:

20800

Hom.:

124

AF XY:

0.0605

AC XY:

714

AN XY:

11796

show subpopulations

African (AFR)

AF:

0.247

AC:

235

AN:

950

American (AMR)

AF:

0.0333

AC:

AN:

720

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

146

AN:

974

East Asian (EAS)

AF:

0.0154

AC:

AN:

1042

South Asian (SAS)

AF:

0.301

AC:

491

AN:

1630

European-Finnish (FIN)

AF:

0.00111

AC:

AN:

3588

Middle Eastern (MID)

AF:

0.0625

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0135

AC:

146

AN:

10852

Other (OTH)

AF:

0.108

AC:

106

AN:

980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.601

Heterozygous variant carriers

110

138

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:

0.0517

AC:

2427

AN:

46920

Hom.:

154

Cov.:

AF XY:

0.0562

AC XY:

1212

AN XY:

21550

show subpopulations

African (AFR)

AF:

0.134

AC:

1954

AN:

14538

American (AMR)

AF:

0.0109

AC:

AN:

4666

Ashkenazi Jewish (ASJ)

AF:

0.0414

AC:

AN:

1426

East Asian (EAS)

AF:

0.00490

AC:

AN:

1430

South Asian (SAS)

AF:

0.179

AC:

259

AN:

1448

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1054

Middle Eastern (MID)

AF:

0.0385

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00311

AC:

AN:

21538

Other (OTH)

AF:

0.0446

AC:

AN:

628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.591

Heterozygous variant carriers

128

191

255

319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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-TTATATATATATATATA

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