X-74591847-A-T

Position:

• chrX-74591847-A-T

Variant summary

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

The NM_016120.4(RLIM):​c.1468T>A​(p.Ser490Thr) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RLIM NM_016120.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66

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=0.1538032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RLIM	NM_016120.4	c.1468T>A	p.Ser490Thr	missense_variant	4/4	ENST00000332687.11
RLIM	NM_183353.3	c.1468T>A	p.Ser490Thr	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RLIM	ENST00000332687.11	c.1468T>A	p.Ser490Thr	missense_variant	4/4	1	NM_016120.4	P1
RLIM	ENST00000349225.2	c.1468T>A	p.Ser490Thr	missense_variant	5/5	2		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

Mar 30, 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; 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	0.073
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.67
DEOGEN2	Benign	0.14	T;T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.89	N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.65	N;N
REVEL	Benign	0.15
Sift	Benign	0.20	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.010	B;B
Vest4		0.33
MutPred		0.21		Loss of phosphorylation at S490 (P = 0.0736);Loss of phosphorylation at S490 (P = 0.0736);
MVP		0.91
MPC		0.68
ClinPred		0.13	T
GERP RS		4.0
Varity_R		0.15
gMVP		0.34

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-73811682;