13-49737789-C-T

Variant names:

• chr13-49737789-C-T
• rs2181185
• NM_002267.4:c.115-4743G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002267.4(KPNA3):​c.115-4743G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,098 control chromosomes in the GnomAD database, including 54,565 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 0.85 (54565 hom., cov: 31)
• Consequence: KPNA3 NM_002267.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA3	NM_002267.4	c.115-4743G>A		intron_variant	Intron 2 of 16	ENST00000261667.8	NP_002258.2
KPNA3	XM_017020561.2	c.43-4743G>A		intron_variant	Intron 2 of 16		XP_016876050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KPNA3	ENST00000261667.8	c.115-4743G>A		intron_variant	Intron 2 of 16	1	NM_002267.4	ENSP00000261667.3

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128455 AN: 151980 Hom.: 54516 Cov.: 31

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.845 AC: 128562 AN: 152098 Hom.: 54565 Cov.: 31 AF XY: 0.847 AC XY: 62982 AN XY: 74350

African (AFR) AF: 0.773 AC: 32063 AN: 41468

American (AMR) AF: 0.874 AC: 13361 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2742 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5166 AN: 5176

South Asian (SAS) AF: 0.924 AC: 4461 AN: 4828

European-Finnish (FIN) AF: 0.846 AC: 8951 AN: 10576

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58922 AN: 67978

Other (OTH) AF: 0.832 AC: 1758 AN: 2112

Alfa AF: 0.846 Hom.: 7075

Bravo AF: 0.845

Asia WGS AF: 0.946 AC: 3287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.3
DANN	Benign	0.77
PhyloP100		0.074
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: rs2181185; hg19: chr13-50311925;