rs3782929

Variant names:

• chr13-49742968-G-A
• rs3782929
• NM_002267.4:c.114+3981C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

KPNA3 Gene-Disease associations (from GenCC):

• spastic paraplegia 88, autosomal dominant

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002267.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPNA3	NM_002267.4	MANE Select	c.114+3981C>T		intron	N/A	NP_002258.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPNA3	ENST00000261667.8	TSL:1 MANE Select	c.114+3981C>T		intron	N/A	ENSP00000261667.3	O00505
	KPNA3	ENST00000912491.1		c.114+3981C>T		intron	N/A	ENSP00000582550.1
	KPNA3	ENST00000950770.1		c.114+3981C>T		intron	N/A	ENSP00000620829.1

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

African (AFR) AF: 0.218 AC: 9022 AN: 41452

American (AMR) AF: 0.144 AC: 2197 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0762 AC: 264 AN: 3464

East Asian (EAS) AF: 0.585 AC: 3022 AN: 5164

South Asian (SAS) AF: 0.136 AC: 651 AN: 4778

European-Finnish (FIN) AF: 0.0913 AC: 963 AN: 10544

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0263 AC: 1788 AN: 67930

Other (OTH) AF: 0.103 AC: 217 AN: 2108

Alfa AF: 0.0434 Hom.: 167

Bravo AF: 0.132

Asia WGS AF: 0.314 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		0.047
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3782929; hg19: chr13-50317104;