5-62442993-C-T

Position:

• chr5-62442993-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016338.5(IPO11):​c.149C>T​(p.Thr50Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IPO11 NM_016338.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06

Genes affected

IPO11 (HGNC:20628): (importin 11) Importins, including IPO11, are a members of the karyopherin/importin-beta family of transport receptors (see KPNB1; 602738) that mediate nucleocytoplasmic transport of protein and RNA cargoes (Plafker and Macara, 2000 [PubMed 11032817]).[supplied by OMIM, Sep 2008]

ENSG00000288643 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO11	NM_016338.5	c.149C>T	p.Thr50Ile	missense_variant	3/30	ENST00000325324.11	NP_057422.3
IPO11	NM_001134779.2	c.269C>T	p.Thr90Ile	missense_variant	3/30		NP_001128251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO11	ENST00000325324.11	c.149C>T	p.Thr50Ile	missense_variant	3/30	1	NM_016338.5	ENSP00000316651.6
IPO11	ENST00000424533.5	n.149C>T		non_coding_transcript_exon_variant	3/29	2		ENSP00000395685.1
ENSG00000288643	ENST00000509663.2	n.65-72395C>T		intron_variant		3		ENSP00000502199.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

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

Jan 04, 2024

The c.269C>T (p.T90I) alteration is located in exon 3 (coding exon 3) of the IPO11 gene. This alteration results from a C to T substitution at nucleotide position 269, causing the threonine (T) at amino acid position 90 to be replaced by an isoleucine (I). 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	Uncertain	0.35
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T;T;T;.;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	D;D;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.59	D;D;D;D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	2.0	.;.;M;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.8	D;N;N;D;N
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;D;D
Polyphen		0.20, 0.26	.;.;B;.;B
Vest4		0.56, 0.57
MutPred		0.73		Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);.;
MVP		0.34
MPC		0.41
ClinPred		0.97	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-61738820; COSMIC: COSV105210817; COSMIC: COSV105210817;