Variant 1-228487816-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000305943.9(RNF187):c.328A>T(p.Met110Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000295 in 1,184,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

RNF187
ENST00000305943.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0300

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03612247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF187	NM_001010858.3 linkuse as main transcript	c.328A>T	p.Met110Leu	missense_variant	1/4	ENST00000305943.9	NP_001010858.2	Q5TA31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF187	ENST00000305943.9 linkuse as main transcript	c.328A>T	p.Met110Leu	missense_variant	1/4	1	NM_001010858.3	ENSP00000306396.9		Q5TA31A0A1X7SBW3

Frequencies

GnomAD3 genomes

AF:

0.0000532

AC:

AN:

150362

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00203

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:

0.0000261

AC:

AN:

1034088

Hom.:

Cov.:

AF XY:

0.0000365

AC XY:

AN XY:

492936

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000563

Gnomad4 OTH exome

AF:

0.0000770

GnomAD4 genome

AF:

0.0000532

AC:

AN:

150362

Hom.:

Cov.:

AF XY:

0.0000681

AC XY:

AN XY:

73372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00203

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000680

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.328A>T (p.M110L) alteration is located in exon 1 (coding exon 1) of the RNF187 gene. This alteration results from a A to T substitution at nucleotide position 328, causing the methionine (M) at amino acid position 110 to be replaced by a leucine (L). 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

0.094

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.8

DANN

Benign

0.50

DEOGEN2

Benign

0.010

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.038

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

MutationTaster

Benign

0.71

PrimateAI

Pathogenic

0.90

REVEL

Benign

0.028

Sift4G

Benign

1.0

T;.

Polyphen

0.0

.;B

Vest4

0.22

MutPred

0.29

Loss of methylation at R109 (P = 0.1195);Loss of methylation at R109 (P = 0.1195);

MVP

0.23

ClinPred

0.026

GERP RS

0.68

Varity_R

0.11

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