rs3736830

Positions:

• chr13-49732085-G-C
• chr13-49732085-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.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

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=-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/exons	MANE	Protein	UniProt
KPNA3	NM_002267.4	c.383+286C>G		intron_variant		ENST00000261667.8	NP_002258.2
KPNA3	XM_017020561.2	c.311+286C>G		intron_variant			XP_016876050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPNA3	ENST00000261667.8	c.383+286C>G		intron_variant		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

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.729

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

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: rs3736830; hg19: chr13-50306221;