5-62476739-C-G

Position:

• chr5-62476739-C-G

Variant summary

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

The NM_016338.5(IPO11):​c.814C>G​(p.Leu272Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,369,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: IPO11 NM_016338.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.01

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.814C>G	p.Leu272Val	missense_variant	9/30	ENST00000325324.11	NP_057422.3
IPO11	NM_001134779.2	c.934C>G	p.Leu312Val	missense_variant	9/30		NP_001128251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO11	ENST00000325324.11	c.814C>G	p.Leu272Val	missense_variant	9/30	1	NM_016338.5	ENSP00000316651.6
IPO11	ENST00000424533.5	n.814C>G		non_coding_transcript_exon_variant	9/29	2		ENSP00000395685.1
ENSG00000288643	ENST00000509663.2	n.65-38649C>G		intron_variant		3		ENSP00000502199.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1369036 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 679172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.40e-7

Gnomad4 OTH exome AF: 0.00

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

Mar 26, 2024

The c.934C>G (p.L312V) alteration is located in exon 9 (coding exon 9) of the IPO11 gene. This alteration results from a C to G substitution at nucleotide position 934, causing the leucine (L) at amino acid position 312 to be replaced by a valine (V). 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	0.33
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.96	N;N
REVEL	Benign	0.20
Sift	Benign	0.34	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.60	P;P
Vest4		0.66
MutPred		0.51		Loss of stability (P = 0.063);.;
MVP		0.67
MPC		0.26
ClinPred		0.72	D
GERP RS		5.7
Varity_R		0.21
gMVP		0.42

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: chr5-61772566;