rs2305402

Positions:

• chr3-160509919-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002268.5(KPNA4):​c.1138-48T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00716 in 1,188,270 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.017 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (85 hom.)
• Consequence: KPNA4 NM_002268.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0167 (2537/152294) while in subpopulation AFR AF= 0.0461 (1917/41556). AF 95% confidence interval is 0.0444. There are 57 homozygotes in gnomad4. There are 1246 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2537 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPNA4	NM_002268.5	c.1138-48T>G		intron_variant		ENST00000334256.9	NP_002259.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPNA4	ENST00000334256.9	c.1138-48T>G		intron_variant		1	NM_002268.5	ENSP00000334373.4

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2518 AN: 152178 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00291

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00812 AC: 1900 AN: 234118 Hom.: 17 AF XY: 0.00702 AC XY: 891 AN XY: 126844

Gnomad AFR exome AF: 0.0448

Gnomad AMR exome AF: 0.00612

Gnomad ASJ exome AF: 0.0125

Gnomad EAS exome AF: 0.0249

Gnomad SAS exome AF: 0.00442

Gnomad FIN exome AF: 0.000566

Gnomad NFE exome AF: 0.00280

Gnomad OTH exome AF: 0.00840

GnomAD4 exome AF: 0.00576 AC: 5970 AN: 1035976 Hom.: 85 Cov.: 14 AF XY: 0.00557 AC XY: 2972 AN XY: 533672

Gnomad4 AFR exome AF: 0.0469

Gnomad4 AMR exome AF: 0.00689

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.0392

Gnomad4 SAS exome AF: 0.00371

Gnomad4 FIN exome AF: 0.000586

Gnomad4 NFE exome AF: 0.00271

Gnomad4 OTH exome AF: 0.00995

GnomAD4 genome AF: 0.0167 AC: 2537 AN: 152294 Hom.: 57 Cov.: 32 AF XY: 0.0167 AC XY: 1246 AN XY: 74484

Gnomad4 AFR AF: 0.0461

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.0284

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00291

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0103 Hom.: 8

Bravo AF: 0.0192

Asia WGS AF: 0.0240 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs2305402; hg19: chr3-160227707;