rs3736830

Variant names:

• chr13-49732085-G-C
• rs3736830
• NM_002267.4:c.383+286C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-49732085-G-C
• chr13-49732085-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.383+286C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 151,992 control chromosomes in the GnomAD database, including 41,370 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 0.73 (41370 hom., cov: 31)
• Consequence: KPNA3 NM_002267.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 16 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA3	NM_002267.4	c.383+286C>G		intron_variant	Intron 6 of 16	ENST00000261667.8	NP_002258.2
KPNA3	XM_017020561.2	c.311+286C>G		intron_variant	Intron 6 of 16		XP_016876050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KPNA3	ENST00000261667.8	c.383+286C>G		intron_variant	Intron 6 of 16	1	NM_002267.4	ENSP00000261667.3

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110258 AN: 151876 Hom.: 41347 Cov.: 31

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.726 AC: 110325 AN: 151992 Hom.: 41370 Cov.: 31 AF XY: 0.721 AC XY: 53584 AN XY: 74282

African (AFR) AF: 0.555 AC: 22983 AN: 41392

American (AMR) AF: 0.730 AC: 11160 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2477 AN: 3470

East Asian (EAS) AF: 0.415 AC: 2155 AN: 5188

South Asian (SAS) AF: 0.789 AC: 3804 AN: 4820

European-Finnish (FIN) AF: 0.756 AC: 7971 AN: 10544

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57127 AN: 67972

Other (OTH) AF: 0.729 AC: 1542 AN: 2116

Alfa AF: 0.802 Hom.: 27111

Bravo AF: 0.714

Asia WGS AF: 0.632 AC: 2196 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.5
DANN	Benign	0.74
PhyloP100		-0.30
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: rs3736830; hg19: chr13-50306221;