chr13-49719920-G-A

Variant names:

• chr13-49719920-G-A
• rs2273816
• NM_002267.4:c.727-101C>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.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 NM_002267.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 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.727-101C>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.727-101C>T		intron	N/A	ENSP00000261667.3	O00505
	KPNA3	ENST00000912491.1		c.727-101C>T		intron	N/A	ENSP00000582550.1
	KPNA3	ENST00000950770.1		c.727-101C>T		intron	N/A	ENSP00000620829.1

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

African (AFR) AF: 0.0405 AC: 521 AN: 12866

American (AMR) AF: 0.0695 AC: 1589 AN: 22874

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 2513 AN: 18196

East Asian (EAS) AF: 0.163 AC: 4881 AN: 29948

South Asian (SAS) AF: 0.240 AC: 12969 AN: 54092

European-Finnish (FIN) AF: 0.130 AC: 5798 AN: 44690

Middle Eastern (MID) AF: 0.121 AC: 295 AN: 2444

European-Non Finnish (NFE) AF: 0.142 AC: 51715 AN: 363802

Other (OTH) AF: 0.134 AC: 4008 AN: 29970

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

African (AFR) AF: 0.0381 AC: 1581 AN: 41496

American (AMR) AF: 0.0772 AC: 1179 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 492 AN: 3462

East Asian (EAS) AF: 0.149 AC: 774 AN: 5186

South Asian (SAS) AF: 0.258 AC: 1247 AN: 4824

European-Finnish (FIN) AF: 0.132 AC: 1395 AN: 10552

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9597 AN: 67960

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.128 Hom.: 3822

Bravo AF: 0.0999

Asia WGS AF: 0.176 AC: 612 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.76
PhyloP100		0.036
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: rs2273816; hg19: chr13-50294056;