rs993038219

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 1 publications found

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

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_016338.5. 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
	IPO11	NM_016338.5	MANE Select	c.988A>C	p.Asn330His	missense	Exon 10 of 30	NP_057422.3
	IPO11	NM_001134779.2		c.1108A>C	p.Asn370His	missense	Exon 10 of 30	NP_001128251.1	Q9UI26-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO11	ENST00000325324.11	TSL:1 MANE Select	c.988A>C	p.Asn330His	missense	Exon 10 of 30	ENSP00000316651.6	Q9UI26-1
	IPO11	ENST00000424533.5	TSL:2	n.988A>C		non_coding_transcript_exon	Exon 10 of 29	ENSP00000395685.1	F8WDV0
	ENSG00000288643	ENST00000509663.2	TSL:3	n.65-32128A>C		intron	N/A	ENSP00000502199.1	A0A6Q8PGD0

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

African (AFR) AF: 0.00 AC: 0 AN: 33160

American (AMR) AF: 0.00 AC: 0 AN: 43268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25906

East Asian (EAS) AF: 0.00 AC: 0 AN: 39330

South Asian (SAS) AF: 0.00 AC: 0 AN: 82918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107406

Other (OTH) AF: 0.00 AC: 0 AN: 60008

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.13
Sift	Benign	0.20	T
Sift4G	Benign	0.19	T
Polyphen		0.021	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
Mutation Taster		=83/17	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: rs993038219; hg19: chr5-61779087;