Genetic Variant KPNA5:c.1433-29_1433-14delTATATATATATATATA (chr6-116732074-TTATATATATATATATA-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.1433-29_1433-14delTATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 67,642 control chromosomes in the GnomAD database, including 53 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 0.022 ( 47 hom., cov: 0)

Exomes 𝑓: 0.028 ( 6 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 (AMR) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA5	NM_001366306.2 link	c.1433-29_1433-14delTATATATATATATATA		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_1433-46delTATATATATATATATA		intron_variant	Intron 13 of 13	1	NM_001366306.2	ENSP00000357552.1		O15131

Frequencies

GnomAD3 genomes

AF:

0.0217

AC:

1020

AN:

46908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.00140

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.00483

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.0179

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.0176

GnomAD4 exome

AF:

0.0284

AC:

588

AN:

20734

Hom.:

AF XY:

0.0274

AC XY:

322

AN XY:

11756

show subpopulations

African (AFR)

AF:

0.0242

AC:

AN:

950

American (AMR)

AF:

0.0836

AC:

AN:

706

Ashkenazi Jewish (ASJ)

AF:

0.0227

AC:

AN:

968

East Asian (EAS)

AF:

0.00667

AC:

AN:

1050

South Asian (SAS)

AF:

0.00859

AC:

AN:

1630

European-Finnish (FIN)

AF:

0.0291

AC:

104

AN:

3572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0300

AC:

325

AN:

10818

Other (OTH)

AF:

0.0348

AC:

AN:

976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.403

Heterozygous variant carriers

109

136

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:

0.0218

AC:

1021

AN:

46908

Hom.:

Cov.:

AF XY:

0.0217

AC XY:

468

AN XY:

21548

show subpopulations

African (AFR)

AF:

0.0436

AC:

634

AN:

14528

American (AMR)

AF:

0.00857

AC:

AN:

4666

Ashkenazi Jewish (ASJ)

AF:

0.00140

AC:

AN:

1426

East Asian (EAS)

AF:

0.0105

AC:

AN:

1430

South Asian (SAS)

AF:

0.00483

AC:

AN:

1448

European-Finnish (FIN)

AF:

0.0228

AC:

AN:

1054

Middle Eastern (MID)

AF:

0.0192

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0133

AC:

287

AN:

21536

Other (OTH)

AF:

0.0175

AC:

AN:

628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

114

142

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-TTATATATATATATATATATATATATA

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