rs9511451

Variant names:

• chr13-24804338-A-G
• rs9511451
• NM_031277.3:c.2000A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-24804338-A-G
• chr13-24804338-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4525 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55811 hom.)
• Consequence: RNF17 NM_031277.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246
• Publications: 28 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.2000A>G	p.His667Arg	missense_variant	Exon 15 of 36	ENST00000255324.10	NP_112567.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35119 AN: 152036 Hom.: 4531 Cov.: 32

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

GnomAD2 exomes AF: 0.252 AC: 63083 AN: 250340 AF XY: 0.254

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 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.: 30 AF XY: 0.270 AC XY: 196098 AN XY: 725332

African (AFR) AF: 0.107 AC: 3575 AN: 33424

American (AMR) AF: 0.197 AC: 8816 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 6774 AN: 26088

East Asian (EAS) AF: 0.247 AC: 9784 AN: 39628

South Asian (SAS) AF: 0.186 AC: 16035 AN: 86116

European-Finnish (FIN) AF: 0.299 AC: 15930 AN: 53364

Middle Eastern (MID) AF: 0.248 AC: 1427 AN: 5764

European-Non Finnish (NFE) AF: 0.287 AC: 318124 AN: 1108208

Other (OTH) AF: 0.266 AC: 16001 AN: 60244

GnomAD4 genome AF: 0.231 AC: 35098 AN: 152154 Hom.: 4525 Cov.: 32 AF XY: 0.229 AC XY: 17041 AN XY: 74382

African (AFR) AF: 0.117 AC: 4856 AN: 41516

American (AMR) AF: 0.202 AC: 3081 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 914 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1474 AN: 5172

South Asian (SAS) AF: 0.188 AC: 909 AN: 4826

European-Finnish (FIN) AF: 0.278 AC: 2944 AN: 10578

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.293 AC: 19942 AN: 67988

Other (OTH) AF: 0.228 AC: 481 AN: 2110

Alfa AF: 0.270 Hom.: 20090

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	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.35
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.25
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.024
Sift	Benign	0.41	T
Sift4G	Benign	0.89	T
Polyphen		0.0	B
Vest4		0.014
MPC		0.27
ClinPred		0.0015	T
GERP RS		0.31
Varity_R		0.035
gMVP		0.12
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9511451; hg19: chr13-25378476; COSMIC: COSV55035429;