rs73122634

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001278237.2(RXYLT1):c.-506C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,606,588 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 24 hom. )

Consequence

RXYLT1
NM_001278237.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

RXYLT1 (HGNC:13530): (ribitol xylosyltransferase 1) This gene encodes a type II transmembrane protein that is thought to have glycosyltransferase function. Mutations in this gene result in cobblestone lissencephaly. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

RXYLT1 links:

ENSG00000249753 (HGNC:):

ENSG00000249753 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034768581).

BP6

Variant 12-63781124-C-T is Benign according to our data. Variant chr12-63781124-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00417 (635/152140) while in subpopulation AMR AF= 0.00537 (82/15284). AF 95% confidence interval is 0.00443. There are 1 homozygotes in gnomad4. There are 331 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXYLT1	NM_014254.3 link	c.275C>T	p.Thr92Met	missense_variant	Exon 2 of 6	ENST00000261234.11	NP_055069.1	Q9Y2B1
RXYLT1	NM_001278237.2 link	c.-506C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 6		NP_001265166.1	Q9Y2B1
RXYLT1	XM_047428079.1 link	c.275C>T	p.Thr92Met	missense_variant	Exon 2 of 5		XP_047284035.1
RXYLT1	NM_001278237.2 link	c.-506C>T		5_prime_UTR_variant	Exon 2 of 6		NP_001265166.1	Q9Y2B1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXYLT1	ENST00000261234.11 link	c.275C>T	p.Thr92Met	missense_variant	Exon 2 of 6	1	NM_014254.3	ENSP00000261234.6		Q9Y2B1

Frequencies

GnomAD3 genomes

AF:

0.00418

AC:

635

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0185

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00478

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00471

AC:

1155

AN:

245374

Hom.:

AF XY:

0.00461

AC XY:

612

AN XY:

132854

show subpopulations

Gnomad AFR exome

AF:

0.000566

Gnomad AMR exome

AF:

0.00345

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000204

Gnomad FIN exome

AF:

0.0178

Gnomad NFE exome

AF:

0.00553

Gnomad OTH exome

AF:

0.00404

GnomAD4 exome

AF:

0.00434

AC:

6316

AN:

1454448

Hom.:

Cov.:

AF XY:

0.00410

AC XY:

2963

AN XY:

723426

show subpopulations

Gnomad4 AFR exome

AF:

0.000453

Gnomad4 AMR exome

AF:

0.00364

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000201

Gnomad4 FIN exome

AF:

0.0186

Gnomad4 NFE exome

AF:

0.00443

Gnomad4 OTH exome

AF:

0.00368

GnomAD4 genome

AF:

0.00417

AC:

635

AN:

152140

Hom.:

Cov.:

AF XY:

0.00445

AC XY:

331

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00537

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0185

Gnomad4 NFE

AF:

0.00478

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00357

Hom.:

Bravo

AF:

0.00283

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00470

AC:

570

Asia WGS

AF:

0.000578

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RXYLT1: BP4, BS2 -

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 18, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Apr 20, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0029

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

REVEL

Benign

0.029

Sift

Benign

0.066

Sift4G

Benign

0.098

Polyphen

0.013

Vest4

0.15

MVP

0.048

MPC

0.18

ClinPred

0.013

GERP RS

2.3

Varity_R

0.039

gMVP

0.21

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