Genetic Variant RLIM:p.Asn497Ser (chrX-74591825-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016120.4(RLIM):c.1490A>G(p.Asn497Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000896 in 111,631 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Consequence

RLIM
NM_016120.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

non-syndromic X-linked intellectual disability
Inheritance: XL Classification: DEFINITIVE Submitted by: Illumina
intellectual disability, X-linked 61
Inheritance: XL Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Broad Center for Mendelian Genomics, G2P
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RLIM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11947042).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016120.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RLIM	NM_016120.4	MANE Select	c.1490A>G	p.Asn497Ser	missense	Exon 4 of 4	NP_057204.2
	RLIM	NM_183353.3		c.1490A>G	p.Asn497Ser	missense	Exon 5 of 5	NP_899196.1	Q9NVW2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RLIM	ENST00000332687.11	TSL:1 MANE Select	c.1490A>G	p.Asn497Ser	missense	Exon 4 of 4	ENSP00000328059.6	Q9NVW2-1
RLIM	ENST00000349225.2	TSL:2	c.1490A>G	p.Asn497Ser	missense	Exon 5 of 5	ENSP00000253571.3	Q9NVW2-1
RLIM	ENST00000896517.1		c.1490A>G	p.Asn497Ser	missense	Exon 4 of 4	ENSP00000566576.1

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111631

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111631

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33793

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30700

American (AMR)

AF:

0.00

AC:

AN:

10466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.000281

AC:

AN:

3555

South Asian (SAS)

AF:

0.00

AC:

AN:

2658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6036

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53160

Other (OTH)

AF:

0.00

AC:

AN:

1485

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual disability, X-linked 61 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.27

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.69

M_CAP

Benign

0.0066

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

PhyloP100

2.4

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.8

REVEL

Benign

0.051

Sift

Benign

0.12

Sift4G

Benign

0.21

Polyphen

0.0

Vest4

0.18

MutPred

0.23

Gain of phosphorylation at N497 (P = 2e-04)

MVP

0.40

MPC

0.59

ClinPred

0.079

GERP RS

4.1

Varity_R

0.096

gMVP

0.20

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over