13-24764231-C-T

Variant names:

• chr13-24764231-C-T
• rs1363520105
• NM_031277.3:c.28C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031277.3(RNF17):​c.28C>T​(p.Pro10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P10T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RNF17 NM_031277.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08741233).

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.28C>T	p.Pro10Ser	missense	Exon 1 of 36	NP_112567.2	Q9BXT8-3
	RNF17	NM_001184993.2		c.28C>T	p.Pro10Ser	missense	Exon 1 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.28C>T	p.Pro10Ser	missense	Exon 1 of 36	ENSP00000255324.5	Q9BXT8-3
	RNF17	ENST00000255325.6	TSL:2	c.28C>T	p.Pro10Ser	missense	Exon 1 of 15	ENSP00000255325.6	Q9BXT8-1
	RNF17	ENST00000255326.4	TSL:2	n.31C>T		non_coding_transcript_exon	Exon 1 of 12

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452324 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 721316

African (AFR) AF: 0.00 AC: 0 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39528

South Asian (SAS) AF: 0.00 AC: 0 AN: 85586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104794

Other (OTH) AF: 0.00 AC: 0 AN: 59792

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.033
DANN	Benign	0.84
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.4
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.0080
Sift	Benign	0.042	D
Sift4G	Benign	0.55	T
Polyphen		0.067	B
Vest4		0.11
MutPred		0.37		Gain of catalytic residue at S11 (P = 0.0038)
MVP		0.043
MPC		0.22
ClinPred		0.11	T
GERP RS		0.86
PromoterAI		0.081	Neutral
Varity_R		0.021
gMVP		0.16
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1363520105; hg19: chr13-25338369;