NM_031277.3:c.727A>G

Variant names:

• chr13-24788103-A-G
• rs761737194
• NM_031277.3:c.727A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031277.3(RNF17):​c.727A>G​(p.Ile243Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000971 in 1,596,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: RNF17 NM_031277.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08537921).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031277.3. 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
	RNF17	NM_031277.3	MANE Select	c.727A>G	p.Ile243Val	missense	Exon 7 of 36	NP_112567.2	Q9BXT8-3
	RNF17	NM_001184993.2		c.727A>G	p.Ile243Val	missense	Exon 7 of 36	NP_001171922.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF17	ENST00000255324.10	TSL:2 MANE Select	c.727A>G	p.Ile243Val	missense	Exon 7 of 36	ENSP00000255324.5	Q9BXT8-3
	RNF17	ENST00000255325.6	TSL:2	c.727A>G	p.Ile243Val	missense	Exon 7 of 15	ENSP00000255325.6	Q9BXT8-1
	RNF17	ENST00000255326.4	TSL:2	n.730A>G		non_coding_transcript_exon	Exon 7 of 12

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000868 AC: 20 AN: 230448 AF XY: 0.000104

Gnomad AFR exome AF: 0.0000652

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000157

Gnomad OTH exome AF: 0.000361

GnomAD4 exome AF: 0.000105 AC: 152 AN: 1444762 Hom.: 0 Cov.: 29 AF XY: 0.000107 AC XY: 77 AN XY: 718432

African (AFR) AF: 0.0000620 AC: 2 AN: 32236

American (AMR) AF: 0.00 AC: 0 AN: 39488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25656

East Asian (EAS) AF: 0.00 AC: 0 AN: 39152

South Asian (SAS) AF: 0.00 AC: 0 AN: 82266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.000129 AC: 143 AN: 1107344

Other (OTH) AF: 0.000117 AC: 7 AN: 59726

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000580 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.000132 AC: 16

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.099
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.2
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.039
Sift	Benign	0.098	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.26	B
Vest4		0.28
MVP		0.082
MPC		0.18
ClinPred		0.042	T
GERP RS		3.4
Varity_R		0.040
gMVP		0.17
Mutation Taster		=95/5	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

Other links and lift over

dbSNP: rs761737194; hg19: chr13-25362241;