Variant chr5-170909700-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_022897.5(RANBP17):c.529G>A(p.Ala177Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00254 in 1,594,748 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 14 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 159 hom. )

Consequence

RANBP17
NM_022897.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.65

Variant links:

Genes affected

RANBP17 (HGNC:14428): (RAN binding protein 17) The transport of protein and large RNAs through the nuclear pore complexes (NPC) is an energy-dependent and regulated process. The import of proteins with a nuclear localization signal (NLS) is accomplished by recognition of one or more clusters of basic amino acids by the importin-alpha/beta complex; see MIM 600685 and MIM 602738. The small GTPase RAN (MIM 601179) plays a key role in NLS-dependent protein import. RAN-binding protein-17 is a member of the importin-beta superfamily of nuclear transport receptors.[supplied by OMIM, Jul 2002]

RANBP17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048198104).

BP6

Variant 5-170909700-G-A is Benign according to our data. Variant chr5-170909700-G-A is described in ClinVar as [Benign]. Clinvar id is 3044902.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP17	NM_022897.5 linkuse as main transcript	c.529G>A	p.Ala177Thr	missense_variant	6/28	ENST00000523189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP17	ENST00000523189.6 linkuse as main transcript	c.529G>A	p.Ala177Thr	missense_variant	6/28	1	NM_022897.5	P1	Q9H2T7-1

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

382

AN:

149022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000444

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.0676

Gnomad SAS

AF:

0.00106

Gnomad FIN

AF:

0.000200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000149

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.00523

AC:

1292

AN:

247252

Hom.:

AF XY:

0.00487

AC XY:

652

AN XY:

133846

show subpopulations

Gnomad AFR exome

AF:

0.000568

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.0679

Gnomad SAS exome

AF:

0.000266

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000214

Gnomad OTH exome

AF:

0.00268

GnomAD4 exome

AF:

0.00254

AC:

3671

AN:

1445622

Hom.:

159

Cov.:

AF XY:

0.00248

AC XY:

1783

AN XY:

719988

show subpopulations

Gnomad4 AFR exome

AF:

0.000244

Gnomad4 AMR exome

AF:

0.0000453

Gnomad4 ASJ exome

AF:

0.000116

Gnomad4 EAS exome

AF:

0.0854

Gnomad4 SAS exome

AF:

0.000599

Gnomad4 FIN exome

AF:

0.0000754

Gnomad4 NFE exome

AF:

0.0000936

Gnomad4 OTH exome

AF:

0.00246

GnomAD4 genome

AF:

0.00255

AC:

381

AN:

149126

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

225

AN XY:

72646

show subpopulations

Gnomad4 AFR

AF:

0.000443

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.000290

Gnomad4 EAS

AF:

0.0678

Gnomad4 SAS

AF:

0.00106

Gnomad4 FIN

AF:

0.000200

Gnomad4 NFE

AF:

0.000149

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.00271

Hom.:

Bravo

AF:

0.00265

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00532

AC:

646

Asia WGS

AF:

0.0230

AC:

AN:

3470

EpiCase

AF:

0.000110

EpiControl

AF:

0.000240

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RANBP17-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.0048

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.38

Sift

Uncertain

0.021

Sift4G

Uncertain

0.037

Polyphen

0.87

Vest4

0.81

MVP

0.78

MPC

0.060

ClinPred

0.038

GERP RS

5.4

Varity_R

0.42

gMVP

0.36

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