Genetic Variant RNF187:p.Leu3Phe (chr1-228487495-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001010858.3(RNF187):c.7C>T(p.Leu3Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000262 in 1,129,980 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

RNF187
NM_001010858.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.326

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:

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ACMG classification

Classification made for transcript

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=0.16893631).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF187	NM_001010858.3 link	c.7C>T	p.Leu3Phe	missense_variant	Exon 1 of 4	ENST00000305943.9	NP_001010858.2	Q5TA31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF187	ENST00000305943.9 link	c.7C>T	p.Leu3Phe	missense_variant	Exon 1 of 4	1	NM_001010858.3	ENSP00000306396.9		Q5TA31A0A1X7SBW3

Frequencies

GnomAD3 genomes

AF:

0.000227

AC:

AN:

149728

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000398

Gnomad ASJ

AF:

0.000294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0000999

Gnomad MID

AF:

0.0128

Gnomad NFE

AF:

0.000240

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000268

AC:

263

AN:

980148

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

129

AN XY:

464022

show subpopulations

Gnomad4 AFR exome

AF:

0.000314

Gnomad4 AMR exome

AF:

0.000598

Gnomad4 ASJ exome

AF:

0.000315

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000232

Gnomad4 OTH exome

AF:

0.000139

GnomAD4 genome

AF:

0.000220

AC:

AN:

149832

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

AN XY:

73068

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.000397

Gnomad4 ASJ

AF:

0.000294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0000999

Gnomad4 NFE

AF:

0.000240

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.7C>T (p.L3F) alteration is located in exon 1 (coding exon 1) of the RNF187 gene. This alteration results from a C to T substitution at nucleotide position 7, causing the leucine (L) at amino acid position 3 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.036

.;T

FATHMM_MKL

Benign

0.033

MetaRNN

Benign

0.17

T;T

MutationAssessor

Benign

1.4

.;L

PrimateAI

Pathogenic

0.82

Sift4G

Pathogenic

0.0

D;.

Polyphen

0.95

.;P

Vest4

0.080

MVP

0.65

GERP RS

2.2

Varity_R

0.060

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over