1-43949940-C-A

Variant names:

• chr1-43949940-C-A
• rs367545199
• NM_014652.4:c.608C>A

Variant summary

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

The NM_014652.4(IPO13):​c.608C>A​(p.Pro203Gln) variant causes a missense change involving the alteration of a 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P203L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IPO13 NM_014652.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.82
• Publications: 0 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.608C>A	p.Pro203Gln	missense	Exon 2 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.608C>A	p.Pro203Gln	missense	Exon 2 of 20	ENSP00000361418.3	O94829
	IPO13	ENST00000862671.1		c.608C>A	p.Pro203Gln	missense	Exon 2 of 20	ENSP00000532730.1
	IPO13	ENST00000862663.1		c.626C>A	p.Pro209Gln	missense	Exon 2 of 20	ENSP00000532722.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.069
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.22
Sift	Benign	0.27	T
Sift4G	Uncertain	0.050	T
Polyphen		0.26	B
Vest4		0.80
MutPred		0.38		Loss of helix (P = 0.1299)
MVP		0.67
MPC		0.36
ClinPred		0.64	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.18
gMVP		0.32
Mutation Taster		=51/49	polymorphism

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: rs367545199; hg19: chr1-44415612;