Genetic Variant KPNA5:c.1433-51_1433-14delTATATATATATATATATATATATATATATATATATATA (chr6-116732074-TTATATATATATATATATATATATATATATATATATATA-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001366306.2(KPNA5):c.1433-51_1433-14delTATATATATATATATATATATATATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 67,758 control chromosomes in the GnomAD database, including 7 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 0.000043 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00086 ( 7 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

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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

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.1433-51_1433-14delTATATATATATATATATATATATATATATATATATATA	intron	N/A	NP_001353235.1	O15131
KPNA5	NM_001366304.1		c.1493-51_1493-14delTATATATATATATATATATATATATATATATATATATA	intron	N/A	NP_001353233.1	A0A8V8TMV2
KPNA5	NM_001366305.2		c.1493-51_1493-14delTATATATATATATATATATATATATATATATATATATA	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.1433-61_1433-24delTATATATATATATATATATATATATATATATATATATA	intron	N/A	ENSP00000357552.1	O15131
KPNA5	ENST00000356348.6	TSL:1	c.1433-61_1433-24delTATATATATATATATATATATATATATATATATATATA	intron	N/A	ENSP00000348704.1	O15131
KPNA5	ENST00000937498.1		c.1508-61_1508-24delTATATATATATATATATATATATATATATATATATATA	intron	N/A	ENSP00000607557.1

Frequencies

GnomAD3 genomes

AF:

0.0000426

AC:

AN:

46916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000864

AC:

AN:

20842

Hom.:

AF XY:

0.00127

AC XY:

AN XY:

11818

show subpopulations

African (AFR)

AF:

0.00209

AC:

AN:

958

American (AMR)

AF:

0.00

AC:

AN:

722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

976

East Asian (EAS)

AF:

0.00190

AC:

AN:

1050

South Asian (SAS)

AF:

0.00490

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:

0.000552

AC:

AN:

10870

Other (OTH)

AF:

0.00

AC:

AN:

982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.813

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.0000426

AC:

AN:

46916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

21550

show subpopulations

African (AFR)

AF:

0.000138

AC:

AN:

14518

American (AMR)

AF:

0.00

AC:

AN:

4666

Ashkenazi Jewish (ASJ)

AF:

0.00

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:

0.00

AC:

AN:

21536

Other (OTH)

AF:

0.00

AC:

AN:

626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

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

Publications

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6-116732074-TTATATATATATATATATATATATATATATATATATATATATA-TTATA

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