chrX-74591861-C-A

Position:

• chrX-74591861-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016120.4(RLIM):​c.1454G>T​(p.Ser485Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: RLIM NM_016120.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.694

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21498525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RLIM	NM_016120.4	c.1454G>T	p.Ser485Ile	missense_variant	4/4	ENST00000332687.11	NP_057204.2
RLIM	NM_183353.3	c.1454G>T	p.Ser485Ile	missense_variant	5/5		NP_899196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RLIM	ENST00000332687.11	c.1454G>T	p.Ser485Ile	missense_variant	4/4	1	NM_016120.4	ENSP00000328059	P1
RLIM	ENST00000349225.2	c.1454G>T	p.Ser485Ile	missense_variant	5/5	2		ENSP00000253571	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

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

Oct 28, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	2.4
DANN	Benign	0.96
DEOGEN2	Benign	0.27	T;T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.55	.;T
M_CAP	Pathogenic	0.57	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	0.76	N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.16
Sift	Benign	0.10	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.040	B;B
Vest4		0.22
MutPred		0.37		Loss of phosphorylation at S485 (P = 1e-04);Loss of phosphorylation at S485 (P = 1e-04);
MVP		0.84
MPC		0.88
ClinPred		0.53	D
GERP RS		3.5
Varity_R		0.16
gMVP		0.52

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-73811696;