13-24793206-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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. 14/20 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, single submitter B:1
• Conservation: PhyloP100: -3.00

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

Verdict is Benign. Variant got -14 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 id is 776785.Status of the report is criteria_provided_single_submitter, 1 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF17	NM_031277.3	c.1100A>G	p.Asn367Ser	missense_variant	10/36	ENST00000255324.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF17	ENST00000255324.10	c.1100A>G	p.Asn367Ser	missense_variant	10/36	2	NM_031277.3	P1
RNF17	ENST00000255325.6	c.1100A>G	p.Asn367Ser	missense_variant	10/15	2
RNF17	ENST00000255326.4	n.1103A>G		non_coding_transcript_exon_variant	10/12	2

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

GnomAD3 exomes AF: 0.00294 AC: 739 AN: 251128 Hom.: 12 AF XY: 0.00217 AC XY: 295 AN XY: 135716

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 SAS exome AF: 0.0000653

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

Gnomad4 AFR exome AF: 0.0457

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000324

Gnomad4 OTH exome AF: 0.00235

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

Gnomad4 AFR AF: 0.0424

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00212 Hom.: 11

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

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;T
MetaRNN	Benign	0.0028	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.55	N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.040	N;.
REVEL	Benign	0.17
Sift	Benign	0.54	T;.
Sift4G	Benign	0.57	T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs61748313; hg19: chr13-25367344;