Variant chr3-160527944-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_002268.5(KPNA4):c.556+9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 1,600,856 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 35 hom. )

Consequence

KPNA4
NM_002268.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.444

Variant links:

Genes affected

KPNA4 (HGNC:6397): (karyopherin subunit alpha 4) The nuclear import of karyophilic proteins is directed by short amino acid sequences termed nuclear localization signals (NLSs). Karyopherins, or importins, are cytoplasmic proteins that recognize NLSs and dock NLS-containing proteins to the nuclear pore complex. The protein encoded by this gene shares the sequence similarity with Xenopus importin-alpha and Saccharomyces cerevisiae Srp1. This protein is found to interact with the NLSs of DNA helicase Q1 and SV40 T antigen. [provided by RefSeq, Jul 2008]

KPNA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 3-160527944-T-A is Benign according to our data. Variant chr3-160527944-T-A is described in ClinVar as [Benign]. Clinvar id is 717875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 633 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPNA4	NM_002268.5 linkuse as main transcript	c.556+9A>T		intron_variant		ENST00000334256.9	NP_002259.1	O00629

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPNA4	ENST00000334256.9 linkuse as main transcript	c.556+9A>T		intron_variant		1	NM_002268.5	ENSP00000334373.4		O00629

Frequencies

GnomAD3 genomes

AF:

0.00416

AC:

633

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00679

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00625

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00401

AC:

1004

AN:

250666

Hom.:

AF XY:

0.00434

AC XY:

589

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.000622

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00389

Gnomad FIN exome

AF:

0.00601

Gnomad NFE exome

AF:

0.00553

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00572

AC:

8281

AN:

1448554

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

4158

AN XY:

721436

show subpopulations

Gnomad4 AFR exome

AF:

0.000904

Gnomad4 AMR exome

AF:

0.00247

Gnomad4 ASJ exome

AF:

0.00100

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00432

Gnomad4 FIN exome

AF:

0.00537

Gnomad4 NFE exome

AF:

0.00653

Gnomad4 OTH exome

AF:

0.00445

GnomAD4 genome

AF:

0.00416

AC:

633

AN:

152302

Hom.:

Cov.:

AF XY:

0.00438

AC XY:

326

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00127

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00517

Gnomad4 FIN

AF:

0.00679

Gnomad4 NFE

AF:

0.00625

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00559

Hom.:

Bravo

AF:

0.00349

Asia WGS

AF:

0.000867

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over