dbSNP rs9511451: RNF17:p.His667Arg (chr13-24804338-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031277.3(RNF17):c.2000A>G(p.His667Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,609,650 control chromosomes in the GnomAD database, including 60,336 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.23 ( 4525 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55811 hom. )

Consequence

RNF17
NM_031277.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.246

Variant links:

Genes affected

RNF17 (HGNC:10060): (ring finger protein 17) This gene is similar to a mouse gene that encodes a testis-specific protein containing a RING finger domain. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, May 2010]

RNF17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003488481).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF17	NM_031277.3 link	c.2000A>G	p.His667Arg	missense_variant	Exon 15 of 36	ENST00000255324.10	NP_112567.2	Q9BXT8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF17	ENST00000255324.10 link	c.2000A>G	p.His667Arg	missense_variant	Exon 15 of 36	2	NM_031277.3	ENSP00000255324.5	Q9BXT8-3
RNF17	ENST00000418120 link	c.-29A>G		5_prime_UTR_variant	Exon 2 of 20	5		ENSP00000388892.1	Q5T2J8
RNF17	ENST00000255325.6 link	c.1949+1767A>G		intron_variant	Intron 14 of 14	2		ENSP00000255325.6	Q9BXT8-1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35119

AN:

152036

Hom.:

4531

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.231

GnomAD3 exomes

AF:

0.252

AC:

63083

AN:

250340

Hom.:

8404

AF XY:

0.254

AC XY:

34443

AN XY:

135338

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.256

Gnomad EAS exome

AF:

0.288

Gnomad SAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.267

GnomAD4 exome

AF:

0.272

AC:

396466

AN:

1457496

Hom.:

55811

Cov.:

AF XY:

0.270

AC XY:

196098

AN XY:

725332

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.260

Gnomad4 EAS exome

AF:

0.247

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.299

Gnomad4 NFE exome

AF:

0.287

Gnomad4 OTH exome

AF:

0.266

GnomAD4 genome

AF:

0.231

AC:

35098

AN:

152154

Hom.:

4525

Cov.:

AF XY:

0.229

AC XY:

17041

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.202

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.285

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.278

Gnomad4 NFE

AF:

0.293

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.277

Hom.:

13808

Bravo

AF:

0.222

TwinsUK

AF:

0.281

AC:

1041

ALSPAC

AF:

0.290

AC:

1118

ESP6500AA

AF:

0.120

AC:

526

ESP6500EA

AF:

0.293

AC:

2517

ExAC

AF:

0.252

AC:

30584

Asia WGS

AF:

0.230

AC:

802

AN:

3478

EpiCase

AF:

0.292

EpiControl

AF:

0.286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.9

DANN

Benign

0.35

DEOGEN2

Benign

0.027

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.31

PROVEAN

Benign

0.42

REVEL

Benign

0.024

Sift

Benign

0.41

Sift4G

Benign

0.89

Polyphen

0.0

Vest4

0.014

MPC

0.27

ClinPred

0.0015

GERP RS

0.31

Varity_R

0.035

gMVP

0.12

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over