6-13634458-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005493.3(RANBP9):​c.1768G>A​(p.Glu590Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,474 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

RANBP9
NM_005493.3 missense

Scores

5
5
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RANBP9NM_005493.3 linkc.1768G>A p.Glu590Lys missense_variant Exon 11 of 14 ENST00000011619.6 NP_005484.2 Q96S59-1A0A024QZW3
RANBP9XM_017010149.2 linkc.1102G>A p.Glu368Lys missense_variant Exon 11 of 14 XP_016865638.1
RANBP9XM_047418032.1 linkc.1081G>A p.Glu361Lys missense_variant Exon 11 of 14 XP_047273988.1
RANBP9XM_011514205.3 linkc.1526-1937G>A intron_variant Intron 9 of 11 XP_011512507.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RANBP9ENST00000011619.6 linkc.1768G>A p.Glu590Lys missense_variant Exon 11 of 14 1 NM_005493.3 ENSP00000011619.3 Q96S59-1

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152150
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000438
AC:
11
AN:
251044
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135656
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000287
AC:
42
AN:
1461208
Hom.:
0
Cov.:
30
AF XY:
0.0000316
AC XY:
23
AN XY:
726880
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000985
AC:
15
AN:
152266
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000230
Hom.:
0
Bravo
AF:
0.000155
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000577
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 26, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1768G>A (p.E590K) 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 1768, causing the glutamic acid (E) at amino acid position 590 to be replaced by a lysine (K). 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
0.25
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Pathogenic
0.29
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.045
D
MetaRNN
Uncertain
0.63
D
MetaSVM
Benign
-0.33
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-0.91
N
REVEL
Uncertain
0.39
Sift
Benign
0.32
T
Sift4G
Benign
0.50
T
Polyphen
1.0
D
Vest4
0.84
MVP
0.81
MPC
0.064
ClinPred
0.17
T
GERP RS
6.0
Varity_R
0.31
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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.

Other links and lift over

dbSNP: rs202203748; hg19: chr6-13634690; API