rs1006476921

Variant names:

• chr1-228487495-C-G
• rs1006476921
• NM_001010858.3:c.7C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-228487495-C-G
• chr1-228487495-C-T

Variant summary

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

The NM_001010858.3(RNF187):​c.7C>G​(p.Leu3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000668 in 149,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 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. L3F) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
• Consequence: RNF187 NM_001010858.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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=0.22970355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF187	NM_001010858.3	c.7C>G	p.Leu3Val	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.7C>G	p.Leu3Val	missense_variant	Exon 1 of 4	1	NM_001010858.3	ENSP00000306396.9

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149728 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000668 AC: 1 AN: 149728 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72954

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Benign	0.87
DEOGEN2	Benign	0.013	.;T
FATHMM_MKL	Benign	0.030	N
MetaRNN	Benign	0.23	T;T
MutationAssessor	Benign	0.63	.;N
PrimateAI	Pathogenic	0.80	D
Sift4G	Pathogenic	0.0	D;.
Polyphen		0.63	.;P
Vest4		0.075
MVP		0.65
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.041
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs1006476921; hg19: chr1-228675196;