1-43956950-C-T

Variant names:

• chr1-43956950-C-T
• rs17402858
• NM_014652.4:c.1245C>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_014652.4(IPO13):​c.1245C>T​(p.Asp415Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 1,614,084 control chromosomes in the GnomAD database, including 1,069 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 0.027 (67 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1002 hom.)
• Consequence: IPO13 NM_014652.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

Genes affected

IPO13 (HGNC:16853): (importin 13) This gene encodes a member of the importin-beta family of nuclear transport proteins. The encoded protein mediates the import of specific cargo proteins from the cytoplasm to the nucleus and is dependent on the Ras-related nuclear protein-GTPase system. The encoded protein is also involved in nuclear export of the eukaryotic translation initiation factor 1A.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=-0.062 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0272 (4139/152344) while in subpopulation NFE AF= 0.0395 (2690/68034). AF 95% confidence interval is 0.0383. There are 67 homozygotes in gnomad4. There are 1958 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4139 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO13	NM_014652.4	c.1245C>T	p.Asp415Asp	synonymous_variant	Exon 5 of 20	ENST00000372343.8	NP_055467.3
IPO13	XM_024451069.2	c.342C>T	p.Asp114Asp	synonymous_variant	Exon 4 of 19		XP_024306837.1
IPO13	XM_024451070.2	c.342C>T	p.Asp114Asp	synonymous_variant	Exon 4 of 19		XP_024306838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO13	ENST00000372343.8	c.1245C>T	p.Asp415Asp	synonymous_variant	Exon 5 of 20	1	NM_014652.4	ENSP00000361418.3
IPO13	ENST00000492152.5	n.691C>T		non_coding_transcript_exon_variant	Exon 4 of 6	3
IPO13	ENST00000480902.1	n.-159C>T		upstream_gene_variant		3
IPO13	ENST00000489773.5	n.*106C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0272 AC: 4142 AN: 152226 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.00646

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0320

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0395

Gnomad OTH AF: 0.0296

GnomAD3 exomes AF: 0.0287 AC: 7198 AN: 251110 Hom.: 136 AF XY: 0.0297 AC XY: 4034 AN XY: 135762

Gnomad AFR exome AF: 0.00653

Gnomad AMR exome AF: 0.0175

Gnomad ASJ exome AF: 0.0249

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0285

Gnomad FIN exome AF: 0.0332

Gnomad NFE exome AF: 0.0393

Gnomad OTH exome AF: 0.0293

GnomAD4 exome AF: 0.0352 AC: 51381 AN: 1461740 Hom.: 1002 Cov.: 33 AF XY: 0.0351 AC XY: 25515 AN XY: 727178

Gnomad4 AFR exome AF: 0.00580

Gnomad4 AMR exome AF: 0.0174

Gnomad4 ASJ exome AF: 0.0259

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0309

Gnomad4 FIN exome AF: 0.0349

Gnomad4 NFE exome AF: 0.0387

Gnomad4 OTH exome AF: 0.0323

GnomAD4 genome AF: 0.0272 AC: 4139 AN: 152344 Hom.: 67 Cov.: 32 AF XY: 0.0263 AC XY: 1958 AN XY: 74486

Gnomad4 AFR AF: 0.00645

Gnomad4 AMR AF: 0.0319

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0327

Gnomad4 FIN AF: 0.0328

Gnomad4 NFE AF: 0.0395

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0301 Hom.: 51

Bravo AF: 0.0255

Asia WGS AF: 0.0120 AC: 42 AN: 3478

EpiCase AF: 0.0429

EpiControl AF: 0.0373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.7
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs17402858; hg19: chr1-44422622;