dbSNP rs374955178: RLIM:p.Ser485Arg (chrX-74591860-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016120.4(RLIM):c.1455T>G(p.Ser485Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,093,328 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

RLIM
NM_016120.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.21

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]

RLIM links:

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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=0.12604937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLIM	NM_016120.4 link	c.1455T>G	p.Ser485Arg	missense_variant	Exon 4 of 4	ENST00000332687.11	NP_057204.2	Q9NVW2-1
RLIM	NM_183353.3 link	c.1455T>G	p.Ser485Arg	missense_variant	Exon 5 of 5		NP_899196.1	Q9NVW2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLIM	ENST00000332687.11 link	c.1455T>G	p.Ser485Arg	missense_variant	Exon 4 of 4	1	NM_016120.4	ENSP00000328059.6		Q9NVW2-1
RLIM	ENST00000349225.2 link	c.1455T>G	p.Ser485Arg	missense_variant	Exon 5 of 5	2		ENSP00000253571.3		Q9NVW2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000575

AC:

AN:

174025

Hom.:

AF XY:

0.0000167

AC XY:

AN XY:

59975

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000562

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.15e-7

AC:

AN:

1093328

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

360014

show subpopulations

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:

0.0000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.20

T;T

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.68

.;T

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.6

L;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.24

Sift

Benign

0.35

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.077

B;B

Vest4

0.24

MutPred

0.35

Loss of phosphorylation at S485 (P = 1e-04);Loss of phosphorylation at S485 (P = 1e-04);

MVP

0.91

MPC

0.83

ClinPred

0.10

GERP RS

2.9

Varity_R

0.34

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over