Genetic Variant RNF187:p.Arg109Gly (chr1-228487813-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2

The NM_001010858.3(RNF187):c.325C>G(p.Arg109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000254 in 1,182,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

RNF187
NM_001010858.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.486

Publications

0 publications found

Variant links:

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]

RNF187 links:

ENSG00000293430 (HGNC:):

ENSG00000293430 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM1

In a mutagenesis_site Abolishes ubiquitination by TRIM7; when associated with K-98. (size 0) in uniprot entity RN187_HUMAN

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.325C>G	p.Arg109Gly	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.325C>G	p.Arg109Gly	missense	Exon 1 of 4	ENSP00000306396.9	Q5TA31
	ENSG00000293430	ENST00000739614.1		n.658-6821G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000665

AC:

AN:

150466

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000194

AC:

AN:

1032144

Hom.:

Cov.:

AF XY:

0.00000203

AC XY:

AN XY:

491806

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20398

American (AMR)

AF:

0.00

AC:

AN:

6678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11730

East Asian (EAS)

AF:

0.00

AC:

AN:

20118

South Asian (SAS)

AF:

0.00

AC:

AN:

27188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2582

European-Non Finnish (NFE)

AF:

0.00000226

AC:

AN:

886752

Other (OTH)

AF:

0.00

AC:

AN:

38876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000665

AC:

AN:

150466

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41208

American (AMR)

AF:

0.00

AC:

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67414

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Uncertain

0.055

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.11

FATHMM_MKL

Benign

0.065

MetaRNN

Benign

0.23

MutationAssessor

Benign

0.0

PhyloP100

0.49

PrimateAI

Pathogenic

0.89

Sift4G

Benign

0.13

Polyphen

0.99

Vest4

0.32

MVP

0.72

GERP RS

3.0

PromoterAI

0.080

Neutral

(source)

Varity_R

0.12

gMVP

0.43

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.32

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over