Genetic Variant NM_022897.5:c.506C>G (chr5-170909677-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2656071.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022897.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANBP17	NM_022897.5	MANE Select	c.506C>G	p.Pro169Arg	missense	Exon 6 of 28	NP_075048.1	Q546R4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RANBP17	ENST00000523189.6	TSL:1 MANE Select	c.506C>G	p.Pro169Arg	missense	Exon 6 of 28	ENSP00000427975.1	Q9H2T7-1
RANBP17	ENST00000519130.5	TSL:1	n.517C>G		non_coding_transcript_exon	Exon 6 of 6
RANBP17	ENST00000961946.1		c.506C>G	p.Pro169Arg	missense	Exon 6 of 29	ENSP00000632005.1

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

GnomAD2 exomes

AF:

0.00103

AC:

251

AN:

243908

AF XY:

0.000991

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 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

African (AFR)

AF:

0.000374

AC:

AN:

32118

American (AMR)

AF:

0.00136

AC:

AN:

43496

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

25650

East Asian (EAS)

AF:

0.00

AC:

AN:

38718

South Asian (SAS)

AF:

0.000370

AC:

AN:

83880

European-Finnish (FIN)

AF:

0.000644

AC:

AN:

52790

Middle Eastern (MID)

AF:

0.000704

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00149

AC:

1619

AN:

1083118

Other (OTH)

AF:

0.00102

AC:

AN:

58858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

140

209

279

349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000920

AC:

136

AN:

147884

Hom.:

Cov.:

AF XY:

0.000904

AC XY:

AN XY:

71928

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

40032

American (AMR)

AF:

0.00199

AC:

AN:

14558

Ashkenazi Jewish (ASJ)

AF:

0.00145

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5048

South Asian (SAS)

AF:

0.000212

AC:

AN:

4716

European-Finnish (FIN)

AF:

0.000515

AC:

AN:

9712

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00130

AC:

AN:

67142

Other (OTH)

AF:

0.00147

AC:

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

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

PhyloP100

6.7

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

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over