rs199540262

Variant names:

• chr1-19814495-G-A
• rs199540262
• NM_019062.2:c.607C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-19814495-G-A
• chr1-19814495-G-C
• chr1-19814495-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_019062.2(RNF186):​c.607C>T​(p.Arg203Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,000 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R203Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: RNF186 NM_019062.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.771
• Publications: 0 publications found

Genes affected

RNF186 (HGNC:25978): (ring finger protein 186) Enables ubiquitin-protein transferase activity. Involved in several processes, including intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

RNF186-AS1 (HGNC:41127): (RNF186 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07581076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF186	NM_019062.2	c.607C>T	p.Arg203Trp	missense_variant	Exon 1 of 1	ENST00000375121.4	NP_061935.1
RNF186-AS1	NR_186008.1	n.87G>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF186	ENST00000375121.4	c.607C>T	p.Arg203Trp	missense_variant	Exon 1 of 1	6	NM_019062.2	ENSP00000364263.2
RNF186-AS1	ENST00000454736.2	n.142G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152048 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251240 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1461836 Hom.: 0 Cov.: 30 AF XY: 0.0000275 AC XY: 20 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86244

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111988

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152164 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74416

African (AFR) AF: 0.0000482 AC: 2 AN: 41510

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.607C>T (p.R203W) alteration is located in exon 1 (coding exon 1) of the RNF186 gene. This alteration results from a C to T substitution at nucleotide position 607, causing the arginine (R) at amino acid position 203 to be replaced by a tryptophan (W). 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	0.095
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	20
DANN	Benign	0.65
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.77
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.042
Sift	Benign	0.058	T
Sift4G	Uncertain	0.022	D
Polyphen		0.011	B
Vest4		0.13
MutPred		0.36		Loss of disorder (P = 0.0281);
MVP		0.34
MPC		0.16
ClinPred		0.043	T
GERP RS		2.7
Varity_R		0.045
gMVP		0.15
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs199540262; hg19: chr1-20140988;