Genetic Variant RANBP3:p.Glu558Gln (chr19-5917642-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_007322.3(RANBP3):c.1672G>C(p.Glu558Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,454,448 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E558K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

RANBP3
NM_007322.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.47

Publications

0 publications found

Variant links:

Genes affected

RANBP3 (HGNC:9850): (RAN binding protein 3) This gene encodes a protein with a RanBD1 domain that is found in both the nucleus and cytoplasm. This protein plays a role in nuclear export as part of a heteromeric complex. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

RANBP3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2692284).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007322.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RANBP3	NM_007322.3	MANE Select	c.1672G>C	p.Glu558Gln	missense	Exon 17 of 17	NP_015561.1	Q9H6Z4-1
RANBP3	NM_003624.3		c.1657G>C	p.Glu553Gln	missense	Exon 17 of 17	NP_003615.2	Q9H6Z4-2
RANBP3	NM_007320.3		c.1468G>C	p.Glu490Gln	missense	Exon 16 of 16	NP_015559.2	Q9H6Z4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RANBP3	ENST00000340578.10	TSL:1 MANE Select	c.1672G>C	p.Glu558Gln	missense	Exon 17 of 17	ENSP00000341483.5	Q9H6Z4-1
RANBP3	ENST00000439268.6	TSL:1	c.1657G>C	p.Glu553Gln	missense	Exon 17 of 17	ENSP00000404837.1	Q9H6Z4-2
RANBP3	ENST00000034275.12	TSL:1	c.1468G>C	p.Glu490Gln	missense	Exon 16 of 16	ENSP00000034275.7	Q9H6Z4-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1454448

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

44466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26032

East Asian (EAS)

AF:

0.00

AC:

AN:

39586

South Asian (SAS)

AF:

0.00

AC:

AN:

85602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1110956

Other (OTH)

AF:

0.00

AC:

AN:

60154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.011

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

3.5

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.84

REVEL

Benign

0.083

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.052

Polyphen

0.93

Vest4

0.24

MutPred

0.12

Loss of phosphorylation at T563 (P = 0.2922)

MVP

0.54

MPC

0.48

ClinPred

0.78

GERP RS

5.1

Varity_R

0.17

gMVP

0.15

Mutation Taster

=67/33

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over