rs2273816

Positions:

• chr13-49719920-G-A
• chr13-49719920-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000261667.8(KPNA3):​c.727-101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 730,954 control chromosomes in the GnomAD database, including 8,081 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 0.11 (1154 hom., cov: 32)
  • Exomes 𝑓: 0.15 (6927 hom.)
• Consequence: KPNA3 ENST00000261667.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

Genes affected

KPNA3 (HGNC:6396): (karyopherin subunit alpha 3) 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. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion while larger molecules are transported by an active process. The protein encoded by this gene belongs to the importin alpha family, and is involved in nuclear protein import. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPNA3	NM_002267.4	c.727-101C>T		intron_variant		ENST00000261667.8	NP_002258.2
KPNA3	XM_017020561.2	c.655-101C>T		intron_variant			XP_016876050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPNA3	ENST00000261667.8	c.727-101C>T		intron_variant		1	NM_002267.4	ENSP00000261667	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16713 AN: 151954 Hom.: 1155 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.146 AC: 84289 AN: 578882 Hom.: 6927 AF XY: 0.152 AC XY: 47101 AN XY: 310820

Gnomad4 AFR exome AF: 0.0405

Gnomad4 AMR exome AF: 0.0695

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.110 AC: 16713 AN: 152072 Hom.: 1154 Cov.: 32 AF XY: 0.113 AC XY: 8366 AN XY: 74338

Gnomad4 AFR AF: 0.0381

Gnomad4 AMR AF: 0.0772

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.106

Alfa AF: 0.135 Hom.: 2812

Bravo AF: 0.0999

Asia WGS AF: 0.176 AC: 612 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.76

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: rs2273816; hg19: chr13-50294056;