X-74591744-C-A

Position:

• chrX-74591744-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016120.4(RLIM):​c.1571G>T​(p.Gly524Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RLIM NM_016120.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RLIM	NM_016120.4	c.1571G>T	p.Gly524Val	missense_variant	4/4	ENST00000332687.11	NP_057204.2
RLIM	NM_183353.3	c.1571G>T	p.Gly524Val	missense_variant	5/5		NP_899196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RLIM	ENST00000332687.11	c.1571G>T	p.Gly524Val	missense_variant	4/4	1	NM_016120.4	ENSP00000328059	P1
RLIM	ENST00000349225.2	c.1571G>T	p.Gly524Val	missense_variant	5/5	2		ENSP00000253571	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

May 23, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D;D
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Pathogenic	0.61	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.4	D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.98	D;D
Vest4		0.51
MutPred		0.27		Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);
MVP		0.68
MPC		1.9
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.96
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-73811579;