NM_018085.5:c.39G>A

Variant names:

• chr1-201829248-G-A
• rs1378342947
• NM_018085.5:c.39G>A
• IPO9 p.Leu13Leu

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_018085.5(IPO9):​c.39G>A​(p.Leu13Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,431,704 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: 7.0e-7 (0 hom.)
• Consequence: IPO9 NM_018085.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=2.93 with no splicing effect.

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.39G>A	p.Leu13Leu	synonymous	Exon 1 of 24	NP_060555.2
	IPO9-AS1	NR_046696.1		n.312C>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.39G>A	p.Leu13Leu	synonymous	Exon 1 of 24	ENSP00000354742.4	Q96P70
	IPO9	ENST00000926157.1		c.39G>A	p.Leu13Leu	synonymous	Exon 1 of 25	ENSP00000596216.1
	IPO9	ENST00000926161.1		c.39G>A	p.Leu13Leu	synonymous	Exon 1 of 24	ENSP00000596220.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000481 AC: 1 AN: 208090 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000333

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1431704 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 711204

African (AFR) AF: 0.00 AC: 0 AN: 30640

American (AMR) AF: 0.0000241 AC: 1 AN: 41476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25220

East Asian (EAS) AF: 0.00 AC: 0 AN: 36336

South Asian (SAS) AF: 0.00 AC: 0 AN: 82336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5078

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100382

Other (OTH) AF: 0.00 AC: 0 AN: 59036

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		2.9
PromoterAI		-0.0023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1378342947;

hg19: chr1-201798376;