rs114785852

Variant names:

• chr13-24793154-A-G
• rs114785852
• NM_031277.3:c.1048A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-24793154-A-G
• chr13-24793154-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_031277.3(RNF17):​c.1048A>G​(p.Met350Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,614,100 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0075 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (13 hom.)
• Consequence: RNF17 NM_031277.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.66
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029575527).
• BP6: Variant 13-24793154-A-G is Benign according to our data. Variant chr13-24793154-A-G is described in ClinVar as Benign. ClinVar VariationId is 787941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00749 (1141/152330) while in subpopulation AFR AF = 0.0253 (1054/41582). AF 95% confidence interval is 0.0241. There are 14 homozygotes in GnomAd4. There are 542 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

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.1048A>G	p.Met350Val	missense	Exon 10 of 36	NP_112567.2	Q9BXT8-3
	RNF17	NM_001184993.2		c.1048A>G	p.Met350Val	missense	Exon 10 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.1048A>G	p.Met350Val	missense	Exon 10 of 36	ENSP00000255324.5	Q9BXT8-3
	RNF17	ENST00000255325.6	TSL:2	c.1048A>G	p.Met350Val	missense	Exon 10 of 15	ENSP00000255325.6	Q9BXT8-1
	RNF17	ENST00000255326.4	TSL:2	n.1051A>G		non_coding_transcript_exon	Exon 10 of 12

Frequencies

GnomAD3 genomes AF: 0.00746 AC: 1136 AN: 152212 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

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: 0.000118

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00189 AC: 474 AN: 251318 AF XY: 0.00135

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.000955

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000707 AC: 1034 AN: 1461770 Hom.: 13 Cov.: 31 AF XY: 0.000615 AC XY: 447 AN XY: 727184

African (AFR) AF: 0.0258 AC: 865 AN: 33474

American (AMR) AF: 0.00139 AC: 62 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111938

Other (OTH) AF: 0.00144 AC: 87 AN: 60394

GnomAD4 genome AF: 0.00749 AC: 1141 AN: 152330 Hom.: 14 Cov.: 32 AF XY: 0.00728 AC XY: 542 AN XY: 74486

African (AFR) AF: 0.0253 AC: 1054 AN: 41582

American (AMR) AF: 0.00425 AC: 65 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68028

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00265 Hom.: 8

Bravo AF: 0.00841

ESP6500AA AF: 0.0234 AC: 103

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00242 AC: 294

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0010
DANN	Benign	0.31
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0070	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		-2.7
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.017
Sift	Benign	0.37	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.010
MVP		0.068
MPC		0.22
ClinPred		0.0086	T
GERP RS		-10
Varity_R		0.049
gMVP		0.23
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs114785852; hg19: chr13-25367292;