1-228487556-T-G

Variant names:

• chr1-228487556-T-G
• NM_001010858.3:c.68T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001010858.3(RNF187):​c.68T>G​(p.Val23Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNF187 NM_001010858.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

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]

ENSG00000293430 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010858.3. 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
	RNF187	NM_001010858.3	MANE Select	c.68T>G	p.Val23Gly	missense	Exon 1 of 4	NP_001010858.2	Q5TA31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF187	ENST00000305943.9	TSL:1 MANE Select	c.68T>G	p.Val23Gly	missense	Exon 1 of 4	ENSP00000306396.9	Q5TA31
	ENSG00000293430	ENST00000739614.1		n.658-6564A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1092800 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 533470

African (AFR) AF: 0.00 AC: 0 AN: 21374

American (AMR) AF: 0.00 AC: 0 AN: 15522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14886

East Asian (EAS) AF: 0.00 AC: 0 AN: 16566

South Asian (SAS) AF: 0.00 AC: 0 AN: 46446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2800

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 914310

Other (OTH) AF: 0.00 AC: 0 AN: 40594

GnomAD4 genome Cov.: 32

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	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Benign	0.85
DEOGEN2	Uncertain	0.78	D
FATHMM_MKL	Benign	0.47	N
MetaRNN	Uncertain	0.51	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		1.0
PrimateAI	Pathogenic	0.94	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.46
MVP		0.76
GERP RS		3.4
PromoterAI		0.11	Neutral
Varity_R		0.17
gMVP		0.46
Mutation Taster		=300/0	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

hg19: chr1-228675257;