1-43957301-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_014652.4(IPO13):c.1378C>G(p.Pro460Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IPO13 NM_014652.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, IPO13
• BP4: Computational evidence support a benign effect (MetaRNN=0.16839483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPO13	NM_014652.4	c.1378C>G	p.Pro460Ala	missense_variant	6/20	ENST00000372343.8
IPO13	XM_024451069.2	c.475C>G	p.Pro159Ala	missense_variant	5/19
IPO13	XM_024451070.2	c.475C>G	p.Pro159Ala	missense_variant	5/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPO13	ENST00000372343.8	c.1378C>G	p.Pro460Ala	missense_variant	6/20	1	NM_014652.4	P1
IPO13	ENST00000480902.1	n.193C>G		non_coding_transcript_exon_variant	1/2	3
IPO13	ENST00000492152.5	n.824C>G		non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.1378C>G (p.P460A) alteration is located in exon 6 (coding exon 6) of the IPO13 gene. This alteration results from a C to G substitution at nucleotide position 1378, causing the proline (P) at amino acid position 460 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.0072	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	19
Dann	Benign	0.97
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.019
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.15
Sift	Uncertain	0.027	D
Sift4G	Benign	0.11	T
Polyphen		0.20	B
Vest4		0.28
MutPred		0.47		Loss of glycosylation at P460 (P = 0.0414);
MVP		0.43
MPC		1.2
ClinPred		0.80	D
GERP RS		4.8
Varity_R		0.16
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-44422973;