chr1-88983234-G-A

Position:

chr1-88983234-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001162536.3(RBMXL1):c.593C>T(p.Pro198Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000157 in 1,613,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

RBMXL1
NM_001162536.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51

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:

KYAT3 (HGNC:):

KYAT3 links:

Genome browser will be placed here

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=0.16185513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBMXL1	NM_001162536.3 linkuse as main transcript	c.593C>T	p.Pro198Leu	missense_variant	3/3	ENST00000652648.1	NP_001156008.1	Q96E39
KYAT3	NM_001008661.3 linkuse as main transcript	c.99+5018C>T		intron_variant		ENST00000260508.9	NP_001008661.1	Q6YP21-1B4DW13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBMXL1	ENST00000652648.1 linkuse as main transcript	c.593C>T	p.Pro198Leu	missense_variant	3/3		NM_001162536.3	ENSP00000498248.1		Q96E39
KYAT3	ENST00000260508.9 linkuse as main transcript	c.99+5018C>T		intron_variant		1	NM_001008661.3	ENSP00000260508.4		Q6YP21-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251482

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135910

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:

0.0000462

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000166

AC:

243

AN:

1461054

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

107

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000374

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Nov 27, 2023

The c.593C>T (p.P198L) alteration is located in exon 3 (coding exon 1) of the RBMXL1 gene. This alteration results from a C to T substitution at nucleotide position 593, causing the proline (P) at amino acid position 198 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

Benign

0.099

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.064

T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.5

L;L

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.8

D;D

REVEL

Benign

0.18

Sift

Benign

0.066

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.27

B;B

Vest4

0.22

MVP

0.67

MPC

0.38

ClinPred

0.23

GERP RS

1.5

Varity_R

0.081

gMVP

0.13

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