X-74591786-C-T

Position:

• chrX-74591786-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016120.4(RLIM):​c.1529G>A​(p.Arg510Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,947 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: RLIM NM_016120.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.38

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41261774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RLIM	NM_016120.4	c.1529G>A	p.Arg510Gln	missense_variant	4/4	ENST00000332687.11
RLIM	NM_183353.3	c.1529G>A	p.Arg510Gln	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RLIM	ENST00000332687.11	c.1529G>A	p.Arg510Gln	missense_variant	4/4	1	NM_016120.4	P1
RLIM	ENST00000349225.2	c.1529G>A	p.Arg510Gln	missense_variant	5/5	2		P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097947 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363323

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked 61 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Sep 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.63
DEOGEN2	Benign	0.095	T;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.55	N;N
REVEL	Benign	0.13
Sift	Benign	0.52	T;T
Sift4G	Benign	0.60	T;T
Polyphen		0.98	D;D
Vest4		0.45
MutPred		0.21		Loss of methylation at R510 (P = 0.0286);Loss of methylation at R510 (P = 0.0286);
MVP		0.83
MPC		0.86
ClinPred		0.59	D
GERP RS		5.4
Varity_R		0.16
gMVP		0.77

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: rs1602161588; hg19: chrX-73811621; COSMIC: COSV60325468;