13-24793154-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.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. 14/20 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, single submitter B:1
• Conservation: PhyloP100: -2.66

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=0.0029575527).
• BP6: Variant 13-24793154-A-G is Benign according to our data. Variant chr13-24793154-A-G is described in ClinVar as [Benign]. Clinvar id is 787941.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00749 (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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF17	NM_031277.3	c.1048A>G	p.Met350Val	missense_variant	10/36	ENST00000255324.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF17	ENST00000255324.10	c.1048A>G	p.Met350Val	missense_variant	10/36	2	NM_031277.3	P1
RNF17	ENST00000255325.6	c.1048A>G	p.Met350Val	missense_variant	10/15	2
RNF17	ENST00000255326.4	n.1051A>G		non_coding_transcript_exon_variant	10/12	2

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

GnomAD3 exomes AF: 0.00189 AC: 474 AN: 251318 Hom.: 5 AF XY: 0.00135 AC XY: 183 AN XY: 135824

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 SAS exome AF: 0.0000327

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

Gnomad4 AFR exome AF: 0.0258

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00144

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

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.000875 Hom.: 2

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

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

May 14, 2018

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Computational scores

Source: dbNSFP v4.3

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;T
MetaRNN	Benign	0.0030	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.17	N;.
REVEL	Benign	0.017
Sift	Benign	0.37	T;.
Sift4G	Benign	0.36	T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs114785852; hg19: chr13-25367292;