Genetic Variant KPNA5:c.1433-33_1433-14dupTATATATATATATATATATA (chr6-116732074-T-TTATATATATATATATATATA) – 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.1433-33_1433-14dupTATATATATATATATATATA 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 0.00021 ( 1 hom., cov: 12)

Exomes 𝑓: 0.0 ( 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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new If you want to explore the variant's impact on the transcript NM_001366306.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366306.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KPNA5	NM_001366306.2	MANE Select	c.1433-33_1433-14dupTATATATATATATATATATA	intron	N/A	NP_001353235.1	O15131
KPNA5	NM_001366304.1		c.1493-33_1493-14dupTATATATATATATATATATA	intron	N/A	NP_001353233.1	A0A8V8TMV2
KPNA5	NM_001366305.2		c.1493-33_1493-14dupTATATATATATATATATATA	intron	N/A	NP_001353234.1	A0A8V8TMV2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KPNA5	ENST00000368564.7	TSL:1 MANE Select	c.1433-62_1433-61insTATATATATATATATATATA	intron	N/A	ENSP00000357552.1	O15131
KPNA5	ENST00000356348.6	TSL:1	c.1433-62_1433-61insTATATATATATATATATATA	intron	N/A	ENSP00000348704.1	O15131
KPNA5	ENST00000937498.1		c.1508-62_1508-61insTATATATATATATATATATA	intron	N/A	ENSP00000607557.1

Frequencies

GnomAD3 genomes

AF:

0.000213

AC:

AN:

46910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000689

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000701

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000372

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

20842

Hom.:

AF XY:

0.00

AC XY:

AN XY:

11818

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:

0.00

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

GnomAD4 genome

AF:

0.000213

AC:

AN:

46910

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

21550

show subpopulations

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

African (AFR)

AF:

0.0000689

AC:

AN:

14518

American (AMR)

AF:

0.00

AC:

AN:

4666

Ashkenazi Jewish (ASJ)

AF:

0.000701

AC:

AN:

1426

East Asian (EAS)

AF:

0.00

AC:

AN:

1446

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:

0.000372

AC:

AN:

21530

Other (OTH)

AF:

0.00

AC:

AN:

626

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000206047), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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-TTATATATATATATATATATATATATATATATATATATATATATATATATATATATATATATA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over