5-62467206-T-G

Position:

• chr5-62467206-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016338.5(IPO11):​c.592T>G​(p.Ser198Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IPO11 NM_016338.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.621

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08035204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IPO11	NM_016338.5	c.592T>G	p.Ser198Ala	missense_variant	6/30	ENST00000325324.11	NP_057422.3
IPO11	NM_001134779.2	c.712T>G	p.Ser238Ala	missense_variant	6/30		NP_001128251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IPO11	ENST00000325324.11	c.592T>G	p.Ser198Ala	missense_variant	6/30	1	NM_016338.5	ENSP00000316651.6
IPO11	ENST00000424533.5	n.592T>G		non_coding_transcript_exon_variant	6/29	2		ENSP00000395685.1
ENSG00000288643	ENST00000509663.2	n.65-48182T>G		intron_variant		3		ENSP00000502199.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Nov 12, 2024

The c.712T>G (p.S238A) alteration is located in exon 6 (coding exon 6) of the IPO11 gene. This alteration results from a T to G substitution at nucleotide position 712, causing the serine (S) at amino acid position 238 to be replaced by an alanine (A). 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	0.059
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.54	N;N
REVEL	Benign	0.083
Sift	Benign	0.69	T;T
Sift4G	Benign	0.89	T;T
Polyphen		0.0	B;B
Vest4		0.18
MutPred		0.33		Gain of helix (P = 0.0117);.;
MVP		0.55
MPC		0.16
ClinPred		0.19	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.030
gMVP		0.091

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: chr5-61763033;