NM_031277.3:c.28C>A

Variant names:

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

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>A​(p.Pro10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RNF17 NM_031277.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.09911895).

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>A	p.Pro10Thr	missense	Exon 1 of 36	NP_112567.2	Q9BXT8-3
	RNF17	NM_001184993.2		c.28C>A	p.Pro10Thr	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>A	p.Pro10Thr	missense	Exon 1 of 36	ENSP00000255324.5	Q9BXT8-3
	RNF17	ENST00000255325.6	TSL:2	c.28C>A	p.Pro10Thr	missense	Exon 1 of 15	ENSP00000255325.6	Q9BXT8-1
	RNF17	ENST00000255326.4	TSL:2	n.31C>A		non_coding_transcript_exon	Exon 1 of 12

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250102 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452324 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 721316

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.00 AC: 0 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: 0.00000181 AC: 2 AN: 1104794

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000300 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.023
DANN	Benign	0.73
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.4
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.0090
Sift	Benign	0.060	T
Sift4G	Benign	0.50	T
Polyphen		0.067	B
Vest4		0.12
MutPred		0.31		Gain of catalytic residue at S11 (P = 2e-04)
MVP		0.043
MPC		0.25
ClinPred		0.095	T
GERP RS		0.86
PromoterAI		0.15	Neutral
Varity_R		0.032
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;