5-62483260-A-C

Variant names:

• chr5-62483260-A-C
• rs993038219
• NM_016338.5:c.988A>C

Variant summary

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

The NM_016338.5(IPO11):​c.988A>C​(p.Asn330His) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,450,558 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: 0.0000014 (0 hom.)
• Consequence: IPO11 NM_016338.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.85

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 rank	MANE	Protein	UniProt
IPO11	NM_016338.5	c.988A>C	p.Asn330His	missense_variant	Exon 10 of 30	ENST00000325324.11	NP_057422.3
IPO11	NM_001134779.2	c.1108A>C	p.Asn370His	missense_variant	Exon 10 of 30		NP_001128251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO11	ENST00000325324.11	c.988A>C	p.Asn330His	missense_variant	Exon 10 of 30	1	NM_016338.5	ENSP00000316651.6
IPO11	ENST00000424533.5	n.988A>C		non_coding_transcript_exon_variant	Exon 10 of 29	2		ENSP00000395685.1
ENSG00000288643	ENST00000509663.2	n.65-32128A>C		intron_variant	Intron 1 of 5	3		ENSP00000502199.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450558 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 721008

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: 0.00000181

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

Dec 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1108A>C (p.N370H) alteration is located in exon 10 (coding exon 10) of the IPO11 gene. This alteration results from a A to C substitution at nucleotide position 1108, causing the asparagine (N) at amino acid position 370 to be replaced by a histidine (H). 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	0.41
BayesDel_addAF	Benign	0.0061	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.037	T;.
Eigen	Benign	-0.010
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.13
Sift	Benign	0.20	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.021	B;B
Vest4		0.74
MutPred		0.40		Gain of helix (P = 0.0696);.;
MVP		0.67
MPC		0.53
ClinPred		0.86	D
GERP RS		5.4
Varity_R		0.11
gMVP		0.65

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

LitVar

Other links and lift over

dbSNP: rs993038219; hg19: chr5-61779087;