Genetic Variant KPNA5:c.1433-37_1433-14delTATATATATATATATATATATATA (chr6-116732074-TTATATATATATATATATATATATA-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001366306.2(KPNA5):c.1433-37_1433-14delTATATATATATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0052 in 67,726 control chromosomes in the GnomAD database, including 19 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 0.0025 ( 5 hom., cov: 0)

Exomes 𝑓: 0.011 ( 14 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.

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0112 (233/20812) while in subpopulation EAS AF = 0.0421 (44/1046). AF 95% confidence interval is 0.0322. There are 14 homozygotes in GnomAdExome4. There are 119 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 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.1433-37_1433-14delTATATATATATATATATATATATA	intron	N/A	NP_001353235.1	O15131
KPNA5	NM_001366304.1		c.1493-37_1493-14delTATATATATATATATATATATATA	intron	N/A	NP_001353233.1	A0A8V8TMV2
KPNA5	NM_001366305.2		c.1493-37_1493-14delTATATATATATATATATATATATA	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_1433-38delTATATATATATATATATATATATA	intron	N/A	ENSP00000357552.1	O15131
KPNA5	ENST00000356348.6	TSL:1	c.1433-61_1433-38delTATATATATATATATATATATATA	intron	N/A	ENSP00000348704.1	O15131
KPNA5	ENST00000937498.1		c.1508-61_1508-38delTATATATATATATATATATATATA	intron	N/A	ENSP00000607557.1

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

118

AN:

46914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00282

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00407

Gnomad ASJ

AF:

0.000701

Gnomad EAS

AF:

0.00692

Gnomad SAS

AF:

0.00829

Gnomad FIN

AF:

0.000951

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00153

Gnomad OTH

AF:

0.00160

GnomAD4 exome

AF:

0.0112

AC:

233

AN:

20812

Hom.:

AF XY:

0.0101

AC XY:

119

AN XY:

11802

show subpopulations

African (AFR)

AF:

0.0105

AC:

AN:

950

American (AMR)

AF:

0.0152

AC:

AN:

722

Ashkenazi Jewish (ASJ)

AF:

0.0123

AC:

AN:

974

East Asian (EAS)

AF:

0.0421

AC:

AN:

1046

South Asian (SAS)

AF:

0.0172

AC:

AN:

1628

European-Finnish (FIN)

AF:

0.000836

AC:

AN:

3588

Middle Eastern (MID)

AF:

0.0313

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00994

AC:

108

AN:

10860

Other (OTH)

AF:

0.0153

AC:

AN:

980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

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:

0.00254

AC:

119

AN:

46914

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

AN XY:

21552

show subpopulations

African (AFR)

AF:

0.00289

AC:

AN:

14538

American (AMR)

AF:

0.00407

AC:

AN:

4664

Ashkenazi Jewish (ASJ)

AF:

0.000701

AC:

AN:

1426

East Asian (EAS)

AF:

0.00699

AC:

AN:

1430

South Asian (SAS)

AF:

0.00829

AC:

AN:

1448

European-Finnish (FIN)

AF:

0.000951

AC:

AN:

1052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00153

AC:

AN:

21536

Other (OTH)

AF:

0.00159

AC:

AN:

628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.605

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

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-TTATATATATATATATATA

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