Variant chr5-170909677-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_022897.5(RANBP17):c.506C>G(p.Pro169Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00127 in 1,572,190 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

RANBP17
NM_022897.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.74

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11552614).

BP6

Variant 5-170909677-C-G is Benign according to our data. Variant chr5-170909677-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656071.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP17	NM_022897.5 linkuse as main transcript	c.506C>G	p.Pro169Arg	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.506C>G	p.Pro169Arg	missense_variant	6/28	1	NM_022897.5	P1	Q9H2T7-1

Frequencies

GnomAD3 genomes

AF:

0.000920

AC:

136

AN:

147782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00199

Gnomad ASJ

AF:

0.00145

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.000515

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00130

Gnomad OTH

AF:

0.00149

GnomAD3 exomes

AF:

0.00103

AC:

251

AN:

243908

Hom.:

AF XY:

0.000991

AC XY:

131

AN XY:

132134

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00112

Gnomad ASJ exome

AF:

0.00141

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000475

Gnomad FIN exome

AF:

0.000561

Gnomad NFE exome

AF:

0.00147

Gnomad OTH exome

AF:

0.00153

GnomAD4 exome

AF:

0.00130

AC:

1856

AN:

1424306

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

919

AN XY:

710230

show subpopulations

Gnomad4 AFR exome

AF:

0.000374

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00144

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000370

Gnomad4 FIN exome

AF:

0.000644

Gnomad4 NFE exome

AF:

0.00149

Gnomad4 OTH exome

AF:

0.00102

GnomAD4 genome

AF:

0.000920

AC:

136

AN:

147884

Hom.:

Cov.:

AF XY:

0.000904

AC XY:

AN XY:

71928

show subpopulations

Gnomad4 AFR

AF:

0.000150

Gnomad4 AMR

AF:

0.00199

Gnomad4 ASJ

AF:

0.00145

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000212

Gnomad4 FIN

AF:

0.000515

Gnomad4 NFE

AF:

0.00130

Gnomad4 OTH

AF:

0.00147

Alfa

AF:

0.00125

Hom.:

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00103

AC:

125

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

RANBP17: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.020

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.24

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.017

Polyphen

0.96

Vest4

0.73

MVP

0.83

MPC

0.078

ClinPred

0.081

GERP RS

5.4

Varity_R

0.27

gMVP

0.26

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