Variant X-74591624-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016120.4(RLIM):c.1691A>G(p.Asn564Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,210,326 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.0000036 ( 0 hom. 2 hem. )

Consequence

RLIM
NM_016120.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04265204).

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RLIM	NM_016120.4 linkuse as main transcript	c.1691A>G	p.Asn564Ser	missense_variant	4/4	ENST00000332687.11
RLIM	NM_183353.3 linkuse as main transcript	c.1691A>G	p.Asn564Ser	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RLIM	ENST00000332687.11 linkuse as main transcript	c.1691A>G	p.Asn564Ser	missense_variant	4/4	1	NM_016120.4	P1	Q9NVW2-1
RLIM	ENST00000349225.2 linkuse as main transcript	c.1691A>G	p.Asn564Ser	missense_variant	5/5	2		P1	Q9NVW2-1

Frequencies

GnomAD3 genomes

AF:

0.0000803

AC:

AN:

112116

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34264

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000856

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

183405

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

67875

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1098158

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363518

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000802

AC:

AN:

112168

Hom.:

Cov.:

AF XY:

0.0000583

AC XY:

AN XY:

34326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000855

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000144

ExAC

AF:

0.0000165

AC:

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 18, 2021

The c.1691A>G (p.N564S) alteration is located in exon 5 (coding exon 3) of the RLIM gene. This alteration results from a A to G substitution at nucleotide position 1691, causing the asparagine (N) at amino acid position 564 to be replaced by a serine (S). 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

0.072

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-1.0

CADD

Benign

9.9

DANN

Benign

0.47

DEOGEN2

Benign

0.17

T;T

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.89

.;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.14

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.14

Sift

Benign

0.39

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.043

B;B

Vest4

0.056

MutPred

0.28

Gain of catalytic residue at N564 (P = 0.0486);Gain of catalytic residue at N564 (P = 0.0486);

MVP

0.56

MPC

0.79

ClinPred

0.035

GERP RS

4.3

Varity_R

0.16

gMVP

0.47

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over