Variant 5-170862046-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022897.5(RANBP17):c.13T>C(p.Phe5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000775 in 1,463,894 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 5 hom., cov: 34)

Exomes 𝑓: 0.00039 ( 2 hom. )

Consequence

RANBP17
NM_022897.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004602313).

BP6

Variant 5-170862046-T-C is Benign according to our data. Variant chr5-170862046-T-C is described in ClinVar as [Benign]. Clinvar id is 3056422.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP17	NM_022897.5 linkuse as main transcript	c.13T>C	p.Phe5Leu	missense_variant	1/28	ENST00000523189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP17	ENST00000523189.6 linkuse as main transcript	c.13T>C	p.Phe5Leu	missense_variant	1/28	1	NM_022897.5	P1	Q9H2T7-1

Frequencies

GnomAD3 genomes

AF:

0.00407

AC:

619

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000201

AC:

AN:

69792

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

40402

show subpopulations

Gnomad AFR exome

AF:

0.00569

Gnomad AMR exome

AF:

0.000679

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:

0.00

GnomAD4 exome

AF:

0.000393

AC:

515

AN:

1311716

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

214

AN XY:

646316

show subpopulations

Gnomad4 AFR exome

AF:

0.0148

Gnomad4 AMR exome

AF:

0.000695

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000458

Gnomad4 OTH exome

AF:

0.000991

GnomAD4 genome

AF:

0.00407

AC:

620

AN:

152178

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

300

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0144

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00284

Hom.:

Bravo

AF:

0.00433

ExAC

AF:

0.000261

AC:

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

May 24, 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

0.48

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.00045

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.79

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.91

REVEL

Benign

0.050

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.15

MutPred

0.27

Loss of catalytic residue at F5 (P = 0.0722);

MVP

0.15

MPC

0.028

ClinPred

0.025

GERP RS

2.4

Varity_R

0.078

gMVP

0.16

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