Variant 22-20119021-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001278639.2(RANBP1):c.255T>A(p.His85Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

RANBP1
NM_001278639.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0970

Variant links:

Genes affected

RANBP1 (HGNC:9847): (RAN binding protein 1) This gene encodes a protein that forms a complex with Ras-related nuclear protein (Ran) and metabolizes guanoside triphosphate (GTP). This complex participates in the regulation of the cell cycle by controlling transport of proteins and nucleic acids into the nucleus. There are multiple pseudogenes for this gene on chromosomes 9, 12, 17, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RANBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055039614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP1	NM_001278639.2 linkuse as main transcript	c.255T>A	p.His85Gln	missense_variant	2/6	ENST00000430524.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP1	ENST00000430524.6 linkuse as main transcript	c.255T>A	p.His85Gln	missense_variant	2/6	3	NM_001278639.2	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250862

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460166

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726378

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:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Dec 17, 2023

The c.24T>A (p.H8Q) alteration is located in exon 2 (coding exon 2) of the RANBP1 gene. This alteration results from a T to A substitution at nucleotide position 24, causing the histidine (H) at amino acid position 8 to be replaced by a glutamine (Q). 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

0.081

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Benign

0.84

DEOGEN2

Benign

0.020

T;T;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.48

T;T;T;T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.055

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.2

N;.;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.047

D;.;T;T;T

Sift4G

Benign

0.54

T;T;T;T;T

Polyphen

0.0010

.;.;.;B;.

Vest4

0.20, 0.20, 0.19

MutPred

0.090

.;.;Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);

MVP

0.16

MPC

0.81

ClinPred

0.047

GERP RS

-1.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.072

gMVP

0.73

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