1-88983111-C-A

Position:

chr1-88983111-C-A

Variant summary

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

The NM_001162536.3(RBMXL1):c.716G>T(p.Arg239Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,612,230 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

RBMXL1
NM_001162536.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.30

Variant links:

Genes affected

RBMXL1 (HGNC:25073): (RBMX like 1) This gene represents a retrogene of RNA binding motif protein, X-linked (RBMX), which is located on chromosome X. While all introns in the coding sequence have been processed out compared to the RBMX locus, the ORF is intact and there is specific evidence for transcription at this location. The preservation of the ORF by purifying selection in all Old World monkeys carrying it suggests that this locus is likely to be functional, possibly during male meiosis when X chromosomal genes are silenced or during haploid stages of spermatogenesis. This gene shares 5' exon structure with the cysteine conjugate-beta lyase 2 locus on chromosome 1, but the coding sequences are non-overlapping. Alternative splicing results in two transcript variants. [provided by RefSeq, Jun 2009]

RBMXL1 links:

KYAT3 (HGNC:33238): (kynurenine aminotransferase 3) This gene encodes an aminotransferase that transaminates kynurenine to form kynurenic acid, which is a metabolite of tryptophan. Multiple alternatively spliced transcript variants that encode different proteins have been described for this gene. This gene shares 5' exon structure with the RNA binding motif protein, X-linked-like 1 locus on chromosome 1, but the coding sequences are non-overlapping. [provided by RefSeq, Mar 2017]

KYAT3 links:

Genome browser will be placed here

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	Protein	UniProt
RBMXL1	NM_001162536.3 linkuse as main transcript	c.716G>T	p.Arg239Leu	missense_variant	3/3	ENST00000652648.1	NP_001156008.1
KYAT3	NM_001008661.3 linkuse as main transcript	c.99+5141G>T		intron_variant		ENST00000260508.9	NP_001008661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBMXL1	ENST00000652648.1 linkuse as main transcript	c.716G>T	p.Arg239Leu	missense_variant	3/3		NM_001162536.3	ENSP00000498248	P1
KYAT3	ENST00000260508.9 linkuse as main transcript	c.99+5141G>T		intron_variant		1	NM_001008661.3	ENSP00000260508	A1	Q6YP21-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251434

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460118

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726372

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:

0.0000187

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2023

The c.716G>T (p.R239L) alteration is located in exon 3 (coding exon 1) of the RBMXL1 gene. This alteration results from a G to T substitution at nucleotide position 716, causing the arginine (R) at amino acid position 239 to be replaced by a leucine (L). 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

Uncertain

0.47

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.94

.;D

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.99

D;D

Vest4

0.48

MutPred

0.18

Gain of catalytic residue at R239 (P = 0.0525);Gain of catalytic residue at R239 (P = 0.0525);

MVP

0.81

MPC

1.2

ClinPred

0.99

GERP RS

1.8

Varity_R

0.61

gMVP

0.18

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