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GeneBe

1-43958811-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_014652.4(IPO13):c.1950A>G(p.Thr650=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,613,938 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 61 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 40 hom. )

Consequence

IPO13
NM_014652.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.30
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-43958811-A-G is Benign according to our data. Variant chr1-43958811-A-G is described in ClinVar as [Benign]. Clinvar id is 775544.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.3 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2192/152090) while in subpopulation AFR AF= 0.0503 (2086/41450). AF 95% confidence interval is 0.0485. There are 61 homozygotes in gnomad4. There are 1019 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 2190 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IPO13NM_014652.4 linkuse as main transcriptc.1950A>G p.Thr650= synonymous_variant 11/20 ENST00000372343.8
IPO13XM_024451069.2 linkuse as main transcriptc.1047A>G p.Thr349= synonymous_variant 10/19
IPO13XM_024451070.2 linkuse as main transcriptc.1047A>G p.Thr349= synonymous_variant 10/19

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IPO13ENST00000372343.8 linkuse as main transcriptc.1950A>G p.Thr650= synonymous_variant 11/201 NM_014652.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0144
AC:
2190
AN:
151972
Hom.:
61
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0504
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00484
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.0101
GnomAD3 exomes
AF:
0.00372
AC:
934
AN:
251090
Hom.:
31
AF XY:
0.00284
AC XY:
386
AN XY:
135710
show subpopulations
Gnomad AFR exome
AF:
0.0524
Gnomad AMR exome
AF:
0.00185
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000441
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.00143
AC:
2092
AN:
1461848
Hom.:
40
Cov.:
33
AF XY:
0.00121
AC XY:
879
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0519
Gnomad4 AMR exome
AF:
0.00201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000351
Gnomad4 OTH exome
AF:
0.00341
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0144
AC:
2192
AN:
152090
Hom.:
61
Cov.:
32
AF XY:
0.0137
AC XY:
1019
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0503
Gnomad4 AMR
AF:
0.00484
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00995
Alfa
AF:
0.00640
Hom.:
15
Bravo
AF:
0.0161
Asia WGS
AF:
0.00260
AC:
10
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
Cadd
Benign
1.3
Dann
Benign
0.49
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34228830; hg19: chr1-44424483; API