Variant 6-13634545-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005493.3(RANBP9):c.1681G>A(p.Val561Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,447,718 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RANBP9
NM_005493.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80

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:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
RANBP9	NM_005493.3 link	c.1681G>A	p.Val561Ile	missense_variant	11/14	ENST00000011619.6	NP_005484.2	Q96S59-1A0A024QZW3
RANBP9	XM_017010149.2 link	c.1015G>A	p.Val339Ile	missense_variant	11/14		XP_016865638.1
RANBP9	XM_047418032.1 link	c.994G>A	p.Val332Ile	missense_variant	11/14		XP_047273988.1
RANBP9	XM_011514205.3 link	c.1526-2024G>A		intron_variant			XP_011512507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RANBP9	ENST00000011619.6 link	c.1681G>A	p.Val561Ile	missense_variant	11/14	1	NM_005493.3	ENSP00000011619.3		Q96S59-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1447718

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718962

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.05e-7

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2023

The c.1681G>A (p.V561I) alteration is located in exon 11 (coding exon 11) of the RANBP9 gene. This alteration results from a G to A substitution at nucleotide position 1681, causing the valine (V) at amino acid position 561 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.68

MetaSVM

Uncertain

0.067

MutationAssessor

Uncertain

2.0

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.47

REVEL

Uncertain

0.39

Sift

Benign

0.037

Sift4G

Benign

0.15

Polyphen

1.0

Vest4

0.64

MutPred

0.31

Loss of loop (P = 0.0804);

MVP

0.54

MPC

0.25

ClinPred

0.79

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over