Variant X-74591520-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5

The ENST00000332687.11(RLIM):c.1795C>T(p.Arg599Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R599S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Consequence

RLIM
ENST00000332687.11 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.54

Variant links:

Genes affected

RLIM (HGNC:13429): (ring finger protein, LIM domain interacting) The protein encoded by this gene is a RING-H2 zinc finger protein. It has been shown to be an E3 ubiquitin protein ligase that targets LIM domain binding 1 (LDB1/CLIM), and causes proteasome-dependent degradation of LDB1. This protein and LDB1 are co-repressors of LHX1/LIM-1, a homeodomain transcription factor. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Feb 2009]

RLIM links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1

In a helix (size 7) in uniprot entity RNF12_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in ENST00000332687.11

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.927

PP5

Variant X-74591520-G-A is Pathogenic according to our data. Variant chrX-74591520-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 253089.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-74591520-G-A is described in Lovd as [Pathogenic]. Variant chrX-74591520-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RLIM	NM_016120.4 linkuse as main transcript	c.1795C>T	p.Arg599Cys	missense_variant	4/4	ENST00000332687.11	NP_057204.2
RLIM	NM_183353.3 linkuse as main transcript	c.1795C>T	p.Arg599Cys	missense_variant	5/5		NP_899196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RLIM	ENST00000332687.11 linkuse as main transcript	c.1795C>T	p.Arg599Cys	missense_variant	4/4	1	NM_016120.4	ENSP00000328059	P1	Q9NVW2-1
RLIM	ENST00000349225.2 linkuse as main transcript	c.1795C>T	p.Arg599Cys	missense_variant	5/5	2		ENSP00000253571	P1	Q9NVW2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Intellectual disability, X-linked 61

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.41

T;T

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

.;D

M_CAP

Pathogenic

0.84

MetaRNN

Pathogenic

0.93

D;D

MetaSVM

Uncertain

0.0031

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-7.1

D;D

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.71

MutPred

0.65

Gain of catalytic residue at W600 (P = 0.0059);Gain of catalytic residue at W600 (P = 0.0059);

MVP

0.93

MPC

2.1

ClinPred

1.0

GERP RS

5.4

Varity_R

0.93

gMVP

0.95

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