13-97976720-G-C

Variant names:

• chr13-97976720-G-C
• rs753585799
• NM_002271.6:c.24G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002271.6(IPO5):​c.24G>C​(p.Gln8His) variant causes a missense change. The variant allele was found at a frequency of 0.000000795 in 1,258,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 31)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: IPO5 NM_002271.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87

Genes affected

IPO5 (HGNC:6402): (importin 5) Nucleocytoplasmic transport, a signal- and energy-dependent process, takes place through nuclear pore complexes embedded in the nuclear envelope. The import of proteins containing a nuclear localization signal (NLS) requires the NLS import receptor, a heterodimer of importin alpha and beta subunits also known as karyopherins. Importin alpha binds the NLS-containing cargo in the cytoplasm and importin beta docks the complex at the cytoplasmic side of the nuclear pore complex. In the presence of nucleoside triphosphates and the small GTP binding protein Ran, the complex moves into the nuclear pore complex and the importin subunits dissociate. Importin alpha enters the nucleoplasm with its passenger protein and importin beta remains at the pore. Interactions between importin beta and the FG repeats of nucleoporins are essential in translocation through the pore complex. The protein encoded by this gene is a member of the importin beta family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3659342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.24G>C	p.Gln8His	missense_variant	Exon 4 of 29	ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2	c.24G>C	p.Gln8His	missense_variant	Exon 4 of 29		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000545 AC: 1 AN: 183368 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 101744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000413

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.95e-7 AC: 1 AN: 1258638 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 625674

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: 0.0000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000836 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T;.;.;.;.;T;T;T;T;.;T;T;T;.;T;T;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.87	.;.;D;.;.;D;.;.;.;.;.;.;.;D;D;D;.
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.37	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;.;.;.;.;.;.;.;.;.;.;.;L;.;.;L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.8	D;D;N;D;D;D;D;D;D;D;D;D;N;.;D;N;N
REVEL	Benign	0.17
Sift	Benign	0.035	D;D;D;D;D;D;D;D;D;D;D;D;D;.;T;D;T
Sift4G	Pathogenic	0.0	D;D;T;D;D;D;D;D;D;D;D;D;T;D;T;T;T
Polyphen		1.0, 0.95	.;.;D;.;.;.;.;.;.;.;.;.;P;.;.;P;.
Vest4		0.39, 0.40, 0.42, 0.42
MutPred		0.48		.;.;.;.;.;Gain of helix (P = 0.2059);.;.;.;.;.;.;Gain of helix (P = 0.2059);.;Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);.;
MVP		0.39
MPC		1.0
ClinPred		0.95	D
GERP RS		2.8
Varity_R		0.68
gMVP		0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs753585799; hg19: chr13-98628974;