rs193920920

Variant names:

• chrX-74593054-GT-G
• rs193920920
• NM_016120.4:c.260delA

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_016120.4(RLIM):​c.260delA​(p.Asp87AlafsTer12) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RLIM NM_016120.4 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.64
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: DEFINITIVE Submitted by: Illumina
• intellectual disability, X-linked 61

  Inheritance: XL Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Broad Center for Mendelian Genomics
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 13 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016120.4. 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
	RLIM	NM_016120.4	MANE Select	c.260delA	p.Asp87AlafsTer12	frameshift	Exon 4 of 4	NP_057204.2
	RLIM	NM_183353.3		c.260delA	p.Asp87AlafsTer12	frameshift	Exon 5 of 5	NP_899196.1	Q9NVW2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RLIM	ENST00000332687.11	TSL:1 MANE Select	c.260delA	p.Asp87AlafsTer12	frameshift	Exon 4 of 4	ENSP00000328059.6	Q9NVW2-1
	RLIM	ENST00000349225.2	TSL:2	c.260delA	p.Asp87AlafsTer12	frameshift	Exon 5 of 5	ENSP00000253571.3	Q9NVW2-1
	RLIM	ENST00000896517.1		c.260delA	p.Asp87AlafsTer12	frameshift	Exon 4 of 4	ENSP00000566576.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs193920920;

hg19: chrX-73812889;

COSMIC: COSV60328298;