chr13-24793206-A-G

Variant names:

• chr13-24793206-A-G
• rs61748313
• NM_031277.3:c.1100A>G

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.1100A>G​(p.Asn367Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,614,100 control chromosomes in the GnomAD database, including 91 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 0.012 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (38 hom.)
• Consequence: RNF17 NM_031277.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.00
• Publications: 5 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=0.002772659).
• BP6: Variant 13-24793206-A-G is Benign according to our data. Variant chr13-24793206-A-G is described in ClinVar as Benign. ClinVar VariationId is 776785.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 = 0.0122 (1865/152306) while in subpopulation AFR AF = 0.0424 (1764/41556). AF 95% confidence interval is 0.0408. There are 53 homozygotes in GnomAd4. There are 867 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 53 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.1100A>G	p.Asn367Ser	missense	Exon 10 of 36	NP_112567.2	Q9BXT8-3
	RNF17	NM_001184993.2		c.1100A>G	p.Asn367Ser	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.1100A>G	p.Asn367Ser	missense	Exon 10 of 36	ENSP00000255324.5	Q9BXT8-3
	RNF17	ENST00000255325.6	TSL:2	c.1100A>G	p.Asn367Ser	missense	Exon 10 of 15	ENSP00000255325.6	Q9BXT8-1
	RNF17	ENST00000255326.4	TSL:2	n.1103A>G		non_coding_transcript_exon	Exon 10 of 12

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1859 AN: 152186 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

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: 0.000103

Gnomad OTH AF: 0.0119

GnomAD2 exomes AF: 0.00294 AC: 739 AN: 251128 AF XY: 0.00217

Gnomad AFR exome AF: 0.0421

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.00123 AC: 1803 AN: 1461794 Hom.: 38 Cov.: 32 AF XY: 0.00103 AC XY: 746 AN XY: 727194

African (AFR) AF: 0.0457 AC: 1531 AN: 33470

American (AMR) AF: 0.00179 AC: 80 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1111956

Other (OTH) AF: 0.00235 AC: 142 AN: 60394

GnomAD4 genome AF: 0.0122 AC: 1865 AN: 152306 Hom.: 53 Cov.: 32 AF XY: 0.0116 AC XY: 867 AN XY: 74476

African (AFR) AF: 0.0424 AC: 1764 AN: 41556

American (AMR) AF: 0.00451 AC: 69 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

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: 0.000103 AC: 7 AN: 68018

Other (OTH) AF: 0.0118 AC: 25 AN: 2116

Alfa AF: 0.00482 Hom.: 34

Bravo AF: 0.0142

ESP6500AA AF: 0.0488 AC: 215

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00370 AC: 449

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

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	0.056
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0010
DANN	Benign	0.31
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-3.0
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.17
Sift	Benign	0.54	T
Sift4G	Benign	0.57	T
Polyphen		0.0030	B
Vest4		0.0090
MVP		0.068
MPC		0.17
ClinPred		0.0043	T
GERP RS		-11
Varity_R		0.021
gMVP		0.079
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs61748313; hg19: chr13-25367344;