Genetic Variant RANBP9:p.Lys640Asn (chr6-13632397-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_005493.3(RANBP9):c.1920G>C(p.Lys640Asn) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Consequence

RANBP9
NM_005493.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

Publications

0 publications found

Variant links:

Genes affected

RANBP9 (HGNC:13727): (RAN binding protein 9) This gene encodes a protein that binds RAN, a small GTP binding protein belonging to the RAS superfamily that is essential for the translocation of RNA and proteins through the nuclear pore complex. The protein encoded by this gene has also been shown to interact with several other proteins, including met proto-oncogene, homeodomain interacting protein kinase 2, androgen receptor, and cyclin-dependent kinase 11. [provided by RefSeq, Jul 2008]

RANBP9 links:

NOL7 (HGNC:21040): (nucleolar protein 7) The protein encoded by this gene localizes to the nucleolus, where it maintains nucleolar structure and cell growth rates. The encoded protein also functions as a tumor suppressor and regulator of angiogenesis. The RB tumor suppressor gene recruits transcription factors to this gene and positively regulates its expression. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2015]

NOL7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.756

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005493.3. 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
	RANBP9	NM_005493.3	MANE Select	c.1920G>C	p.Lys640Asn	missense	Exon 12 of 14	NP_005484.2
	NOL7	NM_001317724.2		c.*34C>G		3_prime_UTR	Exon 9 of 9	NP_001304653.1	Q9UMY1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RANBP9	ENST00000011619.6	TSL:1 MANE Select	c.1920G>C	p.Lys640Asn	missense	Exon 12 of 14	ENSP00000011619.3	Q96S59-1
RANBP9	ENST00000940147.1		c.1917G>C	p.Lys639Asn	missense	Exon 12 of 14	ENSP00000610206.1
RANBP9	ENST00000962251.1		c.1896G>C	p.Lys632Asn	missense	Exon 12 of 14	ENSP00000632310.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

249698

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.31

MutationAssessor

Benign

1.6

PhyloP100

2.9

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.57

Sift

Uncertain

0.027

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.69

MutPred

0.57

Loss of methylation at K640 (P = 0.0261)

MVP

0.84

MPC

0.29

ClinPred

0.94

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.58

gMVP

0.59

Mutation Taster

=44/56

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over