5-170909700-G-A

Variant names:

• chr5-170909700-G-A
• rs80184931
• NM_022897.5:c.529G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.0026 (14 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (159 hom.)
• Consequence: RANBP17 NM_022897.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.65

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]

ACMG classification

Our verdict: Benign. The variant received -13 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
RANBP17	NM_022897.5	c.529G>A	p.Ala177Thr	missense_variant	Exon 6 of 28	ENST00000523189.6	NP_075048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANBP17	ENST00000523189.6	c.529G>A	p.Ala177Thr	missense_variant	Exon 6 of 28	1	NM_022897.5	ENSP00000427975.1

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 382 AN: 149022 Hom.: 14 Cov.: 31

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

GnomAD2 exomes AF: 0.00523 AC: 1292 AN: 247252 AF XY: 0.00487

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 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.: 27 AF XY: 0.00248 AC XY: 1783 AN XY: 719988

Gnomad4 AFR exome AF: 0.000244 AC: 8 AN: 32780

Gnomad4 AMR exome AF: 0.0000453 AC: 2 AN: 44142

Gnomad4 ASJ exome AF: 0.000116 AC: 3 AN: 25878

Gnomad4 EAS exome AF: 0.0854 AC: 3347 AN: 39186

Gnomad4 SAS exome AF: 0.000599 AC: 51 AN: 85210

Gnomad4 FIN exome AF: 0.0000754 AC: 4 AN: 53076

Gnomad4 NFE exome AF: 0.0000936 AC: 103 AN: 1099916

Gnomad4 Remaining exome AF: 0.00246 AC: 147 AN: 59722

GnomAD4 genome AF: 0.00255 AC: 381 AN: 149126 Hom.: 14 Cov.: 31 AF XY: 0.00310 AC XY: 225 AN XY: 72646

Gnomad4 AFR AF: 0.000443 AC: 0.000443241 AN: 0.000443241

Gnomad4 AMR AF: 0.000136 AC: 0.000135962 AN: 0.000135962

Gnomad4 ASJ AF: 0.000290 AC: 0.000290023 AN: 0.000290023

Gnomad4 EAS AF: 0.0678 AC: 0.0677663 AN: 0.0677663

Gnomad4 SAS AF: 0.00106 AC: 0.00105574 AN: 0.00105574

Gnomad4 FIN AF: 0.000200 AC: 0.00020016 AN: 0.00020016

Gnomad4 NFE AF: 0.000149 AC: 0.000148566 AN: 0.000148566

Gnomad4 OTH AF: 0.000956 AC: 0.000956023 AN: 0.000956023

Alfa AF: 0.00245 Hom.: 15

Bravo AF: 0.00265

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00532 AC: 646

Asia WGS AF: 0.0230 AC: 80 AN: 3470

EpiCase AF: 0.000110

EpiControl AF: 0.000240

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

RANBP17-related disorder Benign:1

Feb 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	T
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.037	D
Polyphen		0.87	P
Vest4		0.81
MVP		0.78
MPC		0.060
ClinPred		0.038	T
GERP RS		5.4
Varity_R		0.42
gMVP		0.36
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs80184931; hg19: chr5-170336704; COSMIC: COSV66645308; COSMIC: COSV66645308;