rs786205133

Positions:

• chrX-74592248-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The NM_016120.4(RLIM):​c.1067A>G​(p.Tyr356Cys) variant causes a missense change. 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 (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RLIM NM_016120.4 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:3
• Conservation: PhyloP100: 5.85

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837
• PP5: Variant X-74592248-T-C is Pathogenic according to our data. Variant chrX-74592248-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 156224.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-74592248-T-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RLIM	NM_016120.4	c.1067A>G	p.Tyr356Cys	missense_variant	4/4	ENST00000332687.11
RLIM	NM_183353.3	c.1067A>G	p.Tyr356Cys	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RLIM	ENST00000332687.11	c.1067A>G	p.Tyr356Cys	missense_variant	4/4	1	NM_016120.4	P1
RLIM	ENST00000349225.2	c.1067A>G	p.Tyr356Cys	missense_variant	5/5	2		P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

Submissions by phenotype

Global developmental delay Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

-

- -

Intellectual disability, X-linked 61 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 04, 2015

- -

Non-syndromic X-linked intellectual disability Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Department of Clinical Science, University of Bergen

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.59	D;D
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	.;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.021	D;D
Sift4G	Uncertain	0.039	D;D
Polyphen		1.0	D;D
Vest4		0.84
MutPred		0.26		Loss of phosphorylation at Y356 (P = 0.0282);Loss of phosphorylation at Y356 (P = 0.0282);
MVP		0.92
MPC		0.93
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.57
gMVP		0.91

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

Other links and lift over

dbSNP: rs786205133; hg19: chrX-73812083;