Genetic Variant KPNA5:c.1433-41_1433-14delTATATATATATATATATATATATATATA (chr6-116732074-TTATATATATATATATATATATATATATA-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.1433-41_1433-14delTATATATATATATATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 67,716 control chromosomes in the GnomAD database, including 309 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 0.0066 ( 6 hom., cov: 0)

Exomes 𝑓: 0.070 ( 303 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: Benign. The variant received -8 ACMG points.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0991 is higher than 0.05.

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.1433-41_1433-14delTATATATATATATATATATATATATATA	intron	N/A	NP_001353235.1	O15131
KPNA5	NM_001366304.1		c.1493-41_1493-14delTATATATATATATATATATATATATATA	intron	N/A	NP_001353233.1	A0A8V8TMV2
KPNA5	NM_001366305.2		c.1493-41_1493-14delTATATATATATATATATATATATATATA	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_1433-34delTATATATATATATATATATATATATATA	intron	N/A	ENSP00000357552.1	O15131
KPNA5	ENST00000356348.6	TSL:1	c.1433-61_1433-34delTATATATATATATATATATATATATATA	intron	N/A	ENSP00000348704.1	O15131
KPNA5	ENST00000937498.1		c.1508-61_1508-34delTATATATATATATATATATATATATATA	intron	N/A	ENSP00000607557.1

Frequencies

GnomAD3 genomes

AF:

0.00652

AC:

306

AN:

46918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00714

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.000701

Gnomad EAS

AF:

0.00207

Gnomad SAS

AF:

0.0379

Gnomad FIN

AF:

0.00473

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00850

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0704

AC:

1464

AN:

20798

Hom.:

303

AF XY:

0.0660

AC XY:

778

AN XY:

11794

show subpopulations

African (AFR)

AF:

0.0604

AC:

AN:

944

American (AMR)

AF:

0.0167

AC:

AN:

718

Ashkenazi Jewish (ASJ)

AF:

0.0424

AC:

AN:

966

East Asian (EAS)

AF:

0.0114

AC:

AN:

1050

South Asian (SAS)

AF:

0.112

AC:

183

AN:

1628

European-Finnish (FIN)

AF:

0.00557

AC:

AN:

3588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0988

AC:

1073

AN:

10864

Other (OTH)

AF:

0.0676

AC:

AN:

976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.609

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00656

AC:

308

AN:

46918

Hom.:

Cov.:

AF XY:

0.00682

AC XY:

147

AN XY:

21554

show subpopulations

African (AFR)

AF:

0.00199

AC:

AN:

14538

American (AMR)

AF:

0.00622

AC:

AN:

4662

Ashkenazi Jewish (ASJ)

AF:

0.000701

AC:

AN:

1426

East Asian (EAS)

AF:

0.00210

AC:

AN:

1430

South Asian (SAS)

AF:

0.0393

AC:

AN:

1450

European-Finnish (FIN)

AF:

0.00473

AC:

AN:

1056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00850

AC:

183

AN:

21536

Other (OTH)

AF:

0.00

AC:

AN:

628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.611

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 v4.9

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-TTATATATATATATA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over