Variant 5-170909718-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_022897.5(RANBP17):c.547A>T(p.Thr183Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000881 in 1,597,752 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 31)

Exomes 𝑓: 0.00047 ( 7 hom. )

Consequence

RANBP17
NM_022897.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided 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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047468245).

BP6

Variant 5-170909718-A-T is Benign according to our data. Variant chr5-170909718-A-T is described in ClinVar as [Benign]. Clinvar id is 3049366.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00478 (722/150990) while in subpopulation AFR AF= 0.0169 (700/41316). AF 95% confidence interval is 0.0159. There are 4 homozygotes in gnomad4. There are 327 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP17	NM_022897.5 linkuse as main transcript	c.547A>T	p.Thr183Ser	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.547A>T	p.Thr183Ser	missense_variant	6/28	1	NM_022897.5	P1	Q9H2T7-1

Frequencies

GnomAD3 genomes

AF:

0.00479

AC:

722

AN:

150876

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000866

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000888

Gnomad OTH

AF:

0.000967

GnomAD3 exomes

AF:

0.00117

AC:

291

AN:

247914

Hom.:

AF XY:

0.000820

AC XY:

110

AN XY:

134172

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.000504

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:

0.0000178

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000473

AC:

685

AN:

1446762

Hom.:

Cov.:

AF XY:

0.000366

AC XY:

264

AN XY:

720496

show subpopulations

Gnomad4 AFR exome

AF:

0.0181

Gnomad4 AMR exome

AF:

0.000520

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000127

Gnomad4 OTH exome

AF:

0.000870

GnomAD4 genome

AF:

0.00478

AC:

722

AN:

150990

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

327

AN XY:

73734

show subpopulations

Gnomad4 AFR

AF:

0.0169

Gnomad4 AMR

AF:

0.000865

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000888

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000515

Hom.:

Bravo

AF:

0.00543

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00144

AC:

175

Asia WGS

AF:

0.000867

AC:

AN:

3476

EpiCase

AF:

0.000110

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RANBP17-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 23, 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

Benign

0.076

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.2

DANN

Benign

0.76

DEOGEN2

Benign

0.00096

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

MutationTaster

Benign

0.91

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.14

REVEL

Benign

0.030

Sift

Benign

1.0

Sift4G

Benign

0.86

Polyphen

0.0

Vest4

0.24

MutPred

0.19

Gain of disorder (P = 0.0467);

MVP

0.57

MPC

0.025

ClinPred

0.0092

GERP RS

2.7

Varity_R

0.051

gMVP

0.18

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