13-24793338-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031277.3(RNF17):c.1232A>G(p.Asn411Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,432,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: RNF17 NM_031277.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.58

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10857317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF17	NM_031277.3	c.1232A>G	p.Asn411Ser	missense_variant	10/36	ENST00000255324.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF17	ENST00000255324.10	c.1232A>G	p.Asn411Ser	missense_variant	10/36	2	NM_031277.3	P1
RNF17	ENST00000255325.6	c.1232A>G	p.Asn411Ser	missense_variant	10/15	2
RNF17	ENST00000255326.4	n.1235A>G		non_coding_transcript_exon_variant	10/12	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432064 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 710442

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.09e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.1232A>G (p.N411S) alteration is located in exon 10 (coding exon 10) of the RNF17 gene. This alteration results from a A to G substitution at nucleotide position 1232, causing the asparagine (N) at amino acid position 411 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.068	T;.
Eigen	Benign	0.099
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	0.86	N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.0	N;.
REVEL	Benign	0.086
Sift	Uncertain	0.015	D;.
Sift4G	Uncertain	0.020	D;D
Polyphen		0.90	P;.
Vest4		0.18
MutPred		0.34		Gain of catalytic residue at E406 (P = 0.011);Gain of catalytic residue at E406 (P = 0.011);
MVP		0.12
MPC		0.71
ClinPred		0.81	D
GERP RS		5.3
Varity_R		0.12
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-25367476;