X-74591874-AACTGGAACTAGG-AACTGGAACTAGGACTGGAACTAGG

Variant names:

• chrX-74591874-A-AACTGGAACTAGG
• rs1461511590
• NM_016120.4:c.1429_1440dupCCTAGTTCCAGT

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_016120.4(RLIM):​c.1429_1440dupCCTAGTTCCAGT​(p.Ser480_Ser481insProSerSerSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: RLIM NM_016120.4 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.937
• Publications: 0 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), Ambry Genetics, Broad Center for Mendelian Genomics, G2P
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_016120.4

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.1429_1440dupCCTAGTTCCAGT	p.Ser480_Ser481insProSerSerSer	conservative_inframe_insertion	Exon 4 of 4	NP_057204.2
	RLIM	NM_183353.3		c.1429_1440dupCCTAGTTCCAGT	p.Ser480_Ser481insProSerSerSer	conservative_inframe_insertion	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.1429_1440dupCCTAGTTCCAGT	p.Ser480_Ser481insProSerSerSer	conservative_inframe_insertion	Exon 4 of 4	ENSP00000328059.6	Q9NVW2-1
	RLIM	ENST00000349225.2	TSL:2	c.1429_1440dupCCTAGTTCCAGT	p.Ser480_Ser481insProSerSerSer	conservative_inframe_insertion	Exon 5 of 5	ENSP00000253571.3	Q9NVW2-1
	RLIM	ENST00000896517.1		c.1429_1440dupCCTAGTTCCAGT	p.Ser480_Ser481insProSerSerSer	conservative_inframe_insertion	Exon 4 of 4	ENSP00000566576.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.94

Splicing

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

Other links and lift over

dbSNP: rs1461511590; hg19: chrX-73811709;