1-43956950-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014652.4(IPO13):​c.1245C>G​(p.Asp415Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IPO13 NM_014652.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• Publications: 5 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014652.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO13	NM_014652.4	MANE Select	c.1245C>G	p.Asp415Glu	missense	Exon 5 of 20	NP_055467.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO13	ENST00000372343.8	TSL:1 MANE Select	c.1245C>G	p.Asp415Glu	missense	Exon 5 of 20	ENSP00000361418.3	O94829
	IPO13	ENST00000862671.1		c.1245C>G	p.Asp415Glu	missense	Exon 5 of 20	ENSP00000532730.1
	IPO13	ENST00000862663.1		c.1263C>G	p.Asp421Glu	missense	Exon 5 of 20	ENSP00000532722.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 58

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.60
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.062
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.26	T
Polyphen		0.99	D
Vest4		0.59
MutPred		0.62		Gain of loop (P = 0.0851)
MVP		0.73
MPC		1.9
ClinPred		0.98	D
GERP RS		-7.5
Varity_R		0.89
gMVP		0.23
Mutation Taster		=48/52	disease causing

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

Other links and lift over

dbSNP: rs17402858; hg19: chr1-44422622;