rs61751231

Variant names:

• chr12-30637041-C-A
• rs61751231
• NM_006390.4:c.2636G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-30637041-C-A
• chr12-30637041-C-T

Variant summary

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

The NM_006390.4(IPO8):​c.2636G>T​(p.Arg879Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IPO8 NM_006390.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85

Genes affected

IPO8 (HGNC:9853): (importin 8) The importin-alpha/beta complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. The protein encoded by this gene is a member of a class of approximately 20 potential Ran targets that share a sequence motif related to the Ran-binding site of importin-beta. This protein binds to the nuclear pore complex and, along with RanGTP and RANBP1, inhibits the GAP stimulation of the Ran GTPase. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

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
IPO8	NM_006390.4	c.2636G>T	p.Arg879Ile	missense_variant	Exon 22 of 25	ENST00000256079.9	NP_006381.2
IPO8	NM_001190995.2	c.2021G>T	p.Arg674Ile	missense_variant	Exon 18 of 21		NP_001177924.1
IPO8	XM_017018691.3	c.2585G>T	p.Arg862Ile	missense_variant	Exon 22 of 25		XP_016874180.1
IPO8	XM_017018692.2	c.2450G>T	p.Arg817Ile	missense_variant	Exon 21 of 24		XP_016874181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO8	ENST00000256079.9	c.2636G>T	p.Arg879Ile	missense_variant	Exon 22 of 25	1	NM_006390.4	ENSP00000256079.4
IPO8	ENST00000544829.5	c.2021G>T	p.Arg674Ile	missense_variant	Exon 18 of 21	2		ENSP00000444520.1
IPO8	ENST00000535598.1	c.107G>T	p.Arg36Ile	missense_variant	Exon 1 of 3	3		ENSP00000446232.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461788 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727182

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.37	T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.64	P;.
Vest4		0.64
MutPred		0.52		Gain of catalytic residue at T878 (P = 0.0371);.;
MVP		0.57
MPC		0.89
ClinPred		0.99	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
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

LitVar

Other links and lift over

dbSNP: rs61751231; hg19: chr12-30789975; COSMIC: COSV56244046;