Variant X-74591795-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016120.4(RLIM):c.1520G>A(p.Gly507Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,947 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

RLIM
NM_016120.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RLIM	NM_016120.4 linkuse as main transcript	c.1520G>A	p.Gly507Asp	missense_variant	4/4	ENST00000332687.11
RLIM	NM_183353.3 linkuse as main transcript	c.1520G>A	p.Gly507Asp	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RLIM	ENST00000332687.11 linkuse as main transcript	c.1520G>A	p.Gly507Asp	missense_variant	4/4	1	NM_016120.4	P1	Q9NVW2-1
RLIM	ENST00000349225.2 linkuse as main transcript	c.1520G>A	p.Gly507Asp	missense_variant	5/5	2		P1	Q9NVW2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097947

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363315

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 04, 2021

The c.1520G>A (p.G507D) alteration is located in exon 5 (coding exon 3) of the RLIM gene. This alteration results from a G to A substitution at nucleotide position 1520, causing the glycine (G) at amino acid position 507 to be replaced by an aspartic acid (D). Based on data from the Genome Aggregation Database (gnomAD), the RLIM c.1520G>A alteration was not observed, with coverage at this position. This amino acid position is well conserved in available vertebrate species. The p.G507D alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.053

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.12

T;T

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.71

.;T

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

0.88

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.10

N;N

REVEL

Benign

0.14

Sift

Benign

0.54

T;T

Sift4G

Benign

0.91

T;T

Polyphen

0.97

D;D

Vest4

0.68

MutPred

0.19

Loss of methylation at R509 (P = 0.0531);Loss of methylation at R509 (P = 0.0531);

MVP

0.94

MPC

0.96

ClinPred

0.46

GERP RS

5.0

Varity_R

0.21

gMVP

0.64

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