13-49709659-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002267.4(KPNA3):c.945C>T(p.Thr315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00526 in 1,613,820 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (15 hom.)
• Consequence: KPNA3 NM_002267.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 13-49709659-G-A is Benign according to our data. Variant chr13-49709659-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643817.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.
• BS2: High AC in GnomAd at 571 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA3	NM_002267.4	c.945C>T	p.Thr315=	synonymous_variant	12/17	ENST00000261667.8
KPNA3	XM_017020561.2	c.873C>T	p.Thr291=	synonymous_variant	12/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA3	ENST00000261667.8	c.945C>T	p.Thr315=	synonymous_variant	12/17	1	NM_002267.4	P1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 571 AN: 152068 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000894

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00341

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00681

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00565

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00452 AC: 1136 AN: 251420 Hom.: 6 AF XY: 0.00453 AC XY: 616 AN XY: 135890

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00309

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000980

Gnomad FIN exome AF: 0.00910

Gnomad NFE exome AF: 0.00660

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00542 AC: 7920 AN: 1461634 Hom.: 15 Cov.: 30 AF XY: 0.00528 AC XY: 3842 AN XY: 727120

Gnomad4 AFR exome AF: 0.000896

Gnomad4 AMR exome AF: 0.00300

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00143

Gnomad4 FIN exome AF: 0.00867

Gnomad4 NFE exome AF: 0.00619

Gnomad4 OTH exome AF: 0.00460

GnomAD4 genome AF: 0.00375 AC: 571 AN: 152186 Hom.: 2 Cov.: 32 AF XY: 0.00376 AC XY: 280 AN XY: 74394

Gnomad4 AFR AF: 0.000891

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00681

Gnomad4 NFE AF: 0.00565

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00463 Hom.: 2

Bravo AF: 0.00338

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00442

EpiControl AF: 0.00616

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

KPNA3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	5.0
Dann	Benign	0.55

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: rs61749883; hg19: chr13-50283795;