Genetic Variant KPNA5:c.1433-43_1433-14delTATATATATATATATATATATATATATATA (chr6-116732074-TTATATATATATATATATATATATATATATA-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.1433-43_1433-14delTATATATATATATATATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 67,666 control chromosomes in the GnomAD database, including 142 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 0.014 ( 46 hom., cov: 0)

Exomes 𝑓: 0.024 ( 96 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA5	NM_001366306.2 link	c.1433-43_1433-14delTATATATATATATATATATATATATATATA		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_1433-32delTATATATATATATATATATATATATATATA		intron_variant	Intron 13 of 13	1	NM_001366306.2	ENSP00000357552.1		O15131

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

643

AN:

46916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0401

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00729

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00277

Gnomad SAS

AF:

0.00138

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000697

Gnomad OTH

AF:

0.00958

GnomAD4 exome

AF:

0.0244

AC:

506

AN:

20752

Hom.:

AF XY:

0.0202

AC XY:

238

AN XY:

11770

show subpopulations

African (AFR)

AF:

0.187

AC:

178

AN:

952

American (AMR)

AF:

0.0319

AC:

AN:

720

Ashkenazi Jewish (ASJ)

AF:

0.00307

AC:

AN:

976

East Asian (EAS)

AF:

0.0238

AC:

AN:

1050

South Asian (SAS)

AF:

0.0191

AC:

AN:

1624

European-Finnish (FIN)

AF:

0.000836

AC:

AN:

3588

Middle Eastern (MID)

AF:

0.0469

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0181

AC:

196

AN:

10800

Other (OTH)

AF:

0.0450

AC:

AN:

978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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:

0.0137

AC:

641

AN:

46914

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

283

AN XY:

21552

show subpopulations

African (AFR)

AF:

0.0399

AC:

580

AN:

14538

American (AMR)

AF:

0.00729

AC:

AN:

4664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1426

East Asian (EAS)

AF:

0.00280

AC:

AN:

1430

South Asian (SAS)

AF:

0.00138

AC:

AN:

1446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000697

AC:

AN:

21536

Other (OTH)

AF:

0.00955

AC:

AN:

628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.610

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATATATATATA

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