rs752546546

Variant names:

• chr1-201829246-C-A
• rs752546546
• NM_018085.5:c.37C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-201829246-C-A
• chr1-201829246-C-G
• chr1-201829246-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018085.5(IPO9):​c.37C>A​(p.Leu13Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000886 in 1,579,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: IPO9 NM_018085.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.773
• Publications: 0 publications found

Genes affected

IPO9 (HGNC:19425): (importin 9) Enables nuclear import signal receptor activity. Involved in protein import into nucleus. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IPO9-AS1 (HGNC:40892): (IPO9 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09946042).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018085.5. 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
	IPO9	NM_018085.5	MANE Select	c.37C>A	p.Leu13Met	missense	Exon 1 of 24	NP_060555.2
	IPO9-AS1	NR_046696.1		n.314G>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO9	ENST00000361565.9	TSL:1 MANE Select	c.37C>A	p.Leu13Met	missense	Exon 1 of 24	ENSP00000354742.4	Q96P70
	IPO9	ENST00000926157.1		c.37C>A	p.Leu13Met	missense	Exon 1 of 25	ENSP00000596216.1
	IPO9	ENST00000926161.1		c.37C>A	p.Leu13Met	missense	Exon 1 of 24	ENSP00000596220.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000391 AC: 8 AN: 204488 AF XY: 0.0000357

Gnomad AFR exome AF: 0.000101

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000108

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000911 AC: 13 AN: 1427706 Hom.: 0 Cov.: 30 AF XY: 0.0000113 AC XY: 8 AN XY: 709208

African (AFR) AF: 0.00 AC: 0 AN: 30278

American (AMR) AF: 0.000220 AC: 9 AN: 40968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25102

East Asian (EAS) AF: 0.00 AC: 0 AN: 35894

South Asian (SAS) AF: 0.00 AC: 0 AN: 81906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51058

Middle Eastern (MID) AF: 0.000400 AC: 2 AN: 5006

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1098630

Other (OTH) AF: 0.00 AC: 0 AN: 58864

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74342

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000167 AC: 2

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	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.77
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.48	N
REVEL	Benign	0.12
Sift	Benign	0.15	T
Sift4G	Benign	0.26	T
Polyphen		0.054	B
Vest4		0.27
MutPred		0.33		Loss of helix (P = 0.028)
MVP		0.18
MPC		0.57
ClinPred		0.031	T
GERP RS		-1.2
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.083
gMVP		0.15
Mutation Taster		=95/5	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: rs752546546; hg19: chr1-201798374;