rs3782929

Positions:

• chr13-49742968-G-A
• chr13-49742968-G-T

Variant summary

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

The NM_002267.4(KPNA3):​c.114+3981C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 151,902 control chromosomes in the GnomAD database, including 2,179 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 0.12 (2179 hom., cov: 32)
• Consequence: KPNA3 NM_002267.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA3	NM_002267.4	c.114+3981C>T		intron_variant		ENST00000261667.8
KPNA3	XM_017020561.2	c.42+3981C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA3	ENST00000261667.8	c.114+3981C>T		intron_variant		1	NM_002267.4	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18115 AN: 151784 Hom.: 2171 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0762

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0913

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.120 AC: 18154 AN: 151902 Hom.: 2179 Cov.: 32 AF XY: 0.126 AC XY: 9358 AN XY: 74232

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0762

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0913

Gnomad4 NFE AF: 0.0263

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0412 Hom.: 132

Bravo AF: 0.132

Asia WGS AF: 0.314 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.62

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: rs3782929; hg19: chr13-50317104;