X-74591795-C-T

Variant names:

• chrX-74591795-C-T
• NM_016120.4:c.1520G>A

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.91

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]

ACMG classification

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 rank	MANE	Protein	UniProt
RLIM	NM_016120.4	c.1520G>A	p.Gly507Asp	missense_variant	Exon 4 of 4	ENST00000332687.11	NP_057204.2
RLIM	NM_183353.3	c.1520G>A	p.Gly507Asp	missense_variant	Exon 5 of 5		NP_899196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLIM	ENST00000332687.11	c.1520G>A	p.Gly507Asp	missense_variant	Exon 4 of 4	1	NM_016120.4	ENSP00000328059.6
RLIM	ENST00000349225.2	c.1520G>A	p.Gly507Asp	missense_variant	Exon 5 of 5	2		ENSP00000253571.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097947 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363315

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.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jun 04, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	17
DANN	Benign	0.80
DEOGEN2	Benign	0.12	T;T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.71	.;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Uncertain	0.72	T
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	T
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.

Other links and lift over

hg19: chrX-73811630;