1-228493261-G-C

Position:

• chr1-228493261-G-C

Variant summary

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

The NM_001010858.3(RNF187):​c.692G>C​(p.Ser231Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RNF187 NM_001010858.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.137

Genes affected

RNF187 (HGNC:27146): (ring finger protein 187) Enables ubiquitin-protein transferase activity. Involved in positive regulation of transcription, DNA-templated; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.11399743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF187	NM_001010858.3	c.692G>C	p.Ser231Thr	missense_variant	3/4	ENST00000305943.9	NP_001010858.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF187	ENST00000305943.9	c.692G>C	p.Ser231Thr	missense_variant	3/4	1	NM_001010858.3	ENSP00000306396.9
RNF187	ENST00000482739.3	n.570G>C		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397778 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689324

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000560

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Aug 30, 2022

The c.692G>C (p.S231T) alteration is located in exon 3 (coding exon 3) of the RNF187 gene. This alteration results from a G to C substitution at nucleotide position 692, causing the serine (S) at amino acid position 231 to be replaced by a threonine (T). 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	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.54	D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Uncertain	0.65	T
REVEL	Benign	0.11
Sift4G	Pathogenic	0.0	D;.
Polyphen		0.76	.;P
Vest4		0.10
MutPred		0.34		Loss of phosphorylation at S231 (P = 0.0644);Loss of phosphorylation at S231 (P = 0.0644);
MVP		0.081
ClinPred		0.20	T
GERP RS		2.2
Varity_R		0.036
gMVP		0.74

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: chr1-228680962;