Genetic Variant KPNA5:c.1433-33_1433-14delTATATATATATATATATATA (chr6-116732074-TTATATATATATATATATATA-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.1433-33_1433-14delTATATATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 67,686 control chromosomes in the GnomAD database, including 128 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 0.018 ( 61 hom., cov: 0)

Exomes 𝑓: 0.044 ( 67 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 = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA5	NM_001366306.2 link	c.1433-33_1433-14delTATATATATATATATATATA		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_1433-42delTATATATATATATATATATA		intron_variant	Intron 13 of 13	1	NM_001366306.2	ENSP00000357552.1		O15131

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

859

AN:

46910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.00982

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.00691

Gnomad FIN

AF:

0.00951

Gnomad MID

AF:

0.0179

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.0112

GnomAD4 exome

AF:

0.0437

AC:

908

AN:

20776

Hom.:

AF XY:

0.0408

AC XY:

481

AN XY:

11780

show subpopulations

African (AFR)

AF:

0.0136

AC:

AN:

956

American (AMR)

AF:

0.0182

AC:

AN:

716

Ashkenazi Jewish (ASJ)

AF:

0.0512

AC:

AN:

976

East Asian (EAS)

AF:

0.135

AC:

141

AN:

1048

South Asian (SAS)

AF:

0.0154

AC:

AN:

1628

European-Finnish (FIN)

AF:

0.0292

AC:

104

AN:

3566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0477

AC:

517

AN:

10842

Other (OTH)

AF:

0.0459

AC:

AN:

980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

123

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:

0.0182

AC:

855

AN:

46910

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

403

AN XY:

21552

show subpopulations

African (AFR)

AF:

0.0137

AC:

199

AN:

14536

American (AMR)

AF:

0.00858

AC:

AN:

4664

Ashkenazi Jewish (ASJ)

AF:

0.00982

AC:

AN:

1426

East Asian (EAS)

AF:

0.138

AC:

197

AN:

1432

South Asian (SAS)

AF:

0.00691

AC:

AN:

1448

European-Finnish (FIN)

AF:

0.00951

AC:

AN:

1052

Middle Eastern (MID)

AF:

0.0192

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0175

AC:

377

AN:

21532

Other (OTH)

AF:

0.0111

AC:

AN:

628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.567

Heterozygous variant carriers

100

125

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-TTATATATATATATATATATATA

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