Variant X-74591825-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/20 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

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=0.11947042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RLIM	NM_016120.4 linkuse as main transcript	c.1490A>G	p.Asn497Ser	missense_variant	4/4	ENST00000332687.11	NP_057204.2
RLIM	NM_183353.3 linkuse as main transcript	c.1490A>G	p.Asn497Ser	missense_variant	5/5		NP_899196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RLIM	ENST00000332687.11 linkuse as main transcript	c.1490A>G	p.Asn497Ser	missense_variant	4/4	1	NM_016120.4	ENSP00000328059	P1	Q9NVW2-1
RLIM	ENST00000349225.2 linkuse as main transcript	c.1490A>G	p.Asn497Ser	missense_variant	5/5	2		ENSP00000253571	P1	Q9NVW2-1

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111631

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33793

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

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, X-linked 61

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

3billion

Jan 03, 2022

The variant is not observed in the gnomAD v2.1.1 dataset (PM2_M). A missense variant is a common mechanism associated with Tonne-Kalscheuer syndrome (PP2_P). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.27

T;T

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.69

.;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.051

Sift

Benign

0.12

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.0

B;B

Vest4

0.18

MutPred

0.23

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over