Genetic Variant KPNA5:c.1433-31_1433-14dupTATATATATATATATATA (chr6-116732074-T-TTATATATATATATATATA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001366306.2(KPNA5):c.1433-31_1433-14dupTATATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_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 0.00060 ( 0 hom., cov: 12)

Exomes 𝑓: 0.000048 ( 0 hom. )

Failed GnomAD Quality Control

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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA5	NM_001366306.2 link	c.1433-31_1433-14dupTATATATATATATATATA		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.1433-62_1433-61insTATATATATATATATATA		intron_variant	Intron 13 of 13	1	NM_001366306.2	ENSP00000357552.1		O15131

Frequencies

GnomAD3 genomes

AF:

0.000597

AC:

AN:

46896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000620

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00281

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000949

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000650

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000480

AC:

AN:

20842

Hom.:

AF XY:

0.0000846

AC XY:

AN XY:

11818

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:

0.00

AC:

AN:

1050

South Asian (SAS)

AF:

0.00

AC:

AN:

1632

European-Finnish (FIN)

AF:

0.000279

AC:

AN:

3588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

10870

Other (OTH)

AF:

0.00

AC:

AN:

982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000597

AC:

AN:

46896

Hom.:

Cov.:

AF XY:

0.000557

AC XY:

AN XY:

21548

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000619

AC:

AN:

14534

American (AMR)

AF:

0.00

AC:

AN:

4664

Ashkenazi Jewish (ASJ)

AF:

0.00281

AC:

AN:

1426

East Asian (EAS)

AF:

0.00

AC:

AN:

1428

South Asian (SAS)

AF:

0.00

AC:

AN:

1448

European-Finnish (FIN)

AF:

0.000949

AC:

AN:

1054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000650

AC:

AN:

21522

Other (OTH)

AF:

0.00

AC:

AN:

628

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.361

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

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-TTATATATATATATATATATATATATATATATATATATATATATATATATATATATATATA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over