chrX-74591861-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

1
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.694
Variant links:
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]

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ACMG classification

Classification made for transcript

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
RLIMNM_016120.4 linkuse as main transcriptc.1454G>T p.Ser485Ile missense_variant 4/4 ENST00000332687.11 NP_057204.2
RLIMNM_183353.3 linkuse as main transcriptc.1454G>T p.Ser485Ile missense_variant 5/5 NP_899196.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RLIMENST00000332687.11 linkuse as main transcriptc.1454G>T p.Ser485Ile missense_variant 4/41 NM_016120.4 ENSP00000328059 P1Q9NVW2-1
RLIMENST00000349225.2 linkuse as main transcriptc.1454G>T p.Ser485Ile missense_variant 5/52 ENSP00000253571 P1Q9NVW2-1

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
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxOct 28, 2022Not 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; API