Genetic Variant KPNA5:c.1433-47_1433-14delTATATATATATATATATATATATATATATATATA (chr6-116732074-TTATATATATATATATATATATATATATATATATA-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.1433-47_1433-14delTATATATATATATATATATATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 67,744 control chromosomes in the GnomAD database, including 43 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 0.00032 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0062 ( 43 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 (MID) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA5	NM_001366306.2 link	c.1433-47_1433-14delTATATATATATATATATATATATATATATATATA		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_1433-28delTATATATATATATATATATATATATATATATATA		intron_variant	Intron 13 of 13	1	NM_001366306.2	ENSP00000357552.1		O15131

Frequencies

GnomAD3 genomes

AF:

0.000320

AC:

AN:

46914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00415

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000929

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00624

AC:

130

AN:

20830

Hom.:

AF XY:

0.00508

AC XY:

AN XY:

11814

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

958

American (AMR)

AF:

0.00

AC:

AN:

722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

976

East Asian (EAS)

AF:

0.0257

AC:

AN:

1050

South Asian (SAS)

AF:

0.00491

AC:

AN:

1630

European-Finnish (FIN)

AF:

0.00112

AC:

AN:

3586

Middle Eastern (MID)

AF:

0.109

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00653

AC:

AN:

10866

Other (OTH)

AF:

0.0133

AC:

AN:

978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.742

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

<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:

0.000320

AC:

AN:

46914

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

AN XY:

21552

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

14538

American (AMR)

AF:

0.00

AC:

AN:

4664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1426

East Asian (EAS)

AF:

0.00420

AC:

AN:

1430

South Asian (SAS)

AF:

0.00

AC:

AN:

1448

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000929

AC:

AN:

21534

Other (OTH)

AF:

0.00

AC:

AN:

628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.612

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Splicing

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

Publications

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6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATA

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