Genetic Variant KPNA5:c.1433-35_1433-14delTATATATATATATATATATATA (chr6-116732074-TTATATATATATATATATATATA-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.1433-35_1433-14delTATATATATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 67,716 control chromosomes in the GnomAD database, including 88 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 0.012 ( 47 hom., cov: 0)

Exomes 𝑓: 0.031 ( 41 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 (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA5	NM_001366306.2 link	c.1433-35_1433-14delTATATATATATATATATATATA		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_1433-40delTATATATATATATATATATATA		intron_variant	Intron 13 of 13	1	NM_001366306.2	ENSP00000357552.1		O15131

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

585

AN:

46920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00682

Gnomad AMI

AF:

0.0357

Gnomad AMR

AF:

0.00922

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.0138

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.0714

Gnomad NFE

AF:

0.00822

Gnomad OTH

AF:

0.0128

GnomAD4 exome

AF:

0.0308

AC:

641

AN:

20796

Hom.:

AF XY:

0.0305

AC XY:

360

AN XY:

11790

show subpopulations

African (AFR)

AF:

0.00837

AC:

AN:

956

American (AMR)

AF:

0.0125

AC:

AN:

722

Ashkenazi Jewish (ASJ)

AF:

0.0400

AC:

AN:

974

East Asian (EAS)

AF:

0.140

AC:

145

AN:

1036

South Asian (SAS)

AF:

0.0172

AC:

AN:

1630

European-Finnish (FIN)

AF:

0.0204

AC:

AN:

3580

Middle Eastern (MID)

AF:

0.0625

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0282

AC:

306

AN:

10856

Other (OTH)

AF:

0.0297

AC:

AN:

978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

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:

0.0124

AC:

581

AN:

46920

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

285

AN XY:

21556

show subpopulations

African (AFR)

AF:

0.00667

AC:

AN:

14538

American (AMR)

AF:

0.00922

AC:

AN:

4664

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

1426

East Asian (EAS)

AF:

0.124

AC:

178

AN:

1432

South Asian (SAS)

AF:

0.0131

AC:

AN:

1448

European-Finnish (FIN)

AF:

0.0228

AC:

AN:

1054

Middle Eastern (MID)

AF:

0.0769

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00822

AC:

177

AN:

21538

Other (OTH)

AF:

0.0127

AC:

AN:

628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.599

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

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-TTATATATATATATATATATA

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