1-228487813-C-T

Variant names:

• chr1-228487813-C-T
• NM_001010858.3:c.325C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_001010858.3(RNF187):​c.325C>T​(p.Arg109Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000969 in 1,032,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R109G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
• Consequence: RNF187 NM_001010858.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486

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 2 ACMG points.

• PM1: In a modified_residue Asymmetric dimethylarginine; by PRMT1 (size 0) in uniprot entity RN187_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23243755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF187	NM_001010858.3	c.325C>T	p.Arg109Cys	missense_variant	Exon 1 of 4	ENST00000305943.9	NP_001010858.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF187	ENST00000305943.9	c.325C>T	p.Arg109Cys	missense_variant	Exon 1 of 4	1	NM_001010858.3	ENSP00000306396.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.69e-7 AC: 1 AN: 1032144 Hom.: 0 Cov.: 30 AF XY: 0.00000203 AC XY: 1 AN XY: 491806

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: 0.00000113

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.11	.;T
FATHMM_MKL	Benign	0.12	N
MetaRNN	Benign	0.23	T;T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Pathogenic	0.91	D
Sift4G	Uncertain	0.020	D;.
Polyphen		1.0	.;D
Vest4		0.24
MVP		0.71
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.091
gMVP		0.41

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: chr1-228675514;