dbSNP rs938361737: RNF187:p.Ala99Thr (chr1-228487783-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001010858.3(RNF187):c.295G>A(p.Ala99Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,093,224 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

RNF187
NM_001010858.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0550

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1951356).

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.295G>A	p.Ala99Thr	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.295G>A	p.Ala99Thr	missense	Exon 1 of 4	ENSP00000306396.9	Q5TA31
	ENSG00000293430	ENST00000739614.1		n.658-6791C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000154

AC:

AN:

148986

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:

0.000344

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

GnomAD4 exome

AF:

0.000233

AC:

220

AN:

944238

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

111

AN XY:

443188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18354

American (AMR)

AF:

0.00

AC:

AN:

4046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8746

East Asian (EAS)

AF:

0.00

AC:

AN:

13506

South Asian (SAS)

AF:

0.0000536

AC:

AN:

18664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2210

European-Non Finnish (NFE)

AF:

0.000262

AC:

218

AN:

833134

Other (OTH)

AF:

0.0000294

AC:

AN:

33982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

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:

0.000154

AC:

AN:

148986

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

72636

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41066

American (AMR)

AF:

0.00

AC:

AN:

14998

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000344

AC:

AN:

66830

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.000142

Hom.:

Bravo

AF:

0.000181

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

0.11

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0042

FATHMM_MKL

Benign

0.023

MetaRNN

Benign

0.20

MutationAssessor

Benign

0.0

PhyloP100

0.055

PrimateAI

Pathogenic

0.90

Sift4G

Benign

0.51

Polyphen

0.21

Vest4

0.055

MVP

0.63

GERP RS

2.2

PromoterAI

-0.085

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.018

gMVP

0.13

Mutation Taster

=278/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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