rs114036100

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014254.3(RXYLT1):c.469G>A(p.Val157Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,612,092 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 21 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 21 hom. )

Consequence

RXYLT1
NM_014254.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.133

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

muscle-eye-brain disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RXYLT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022054315).

BP6

Variant 12-63802131-G-A is Benign according to our data. Variant chr12-63802131-G-A is described in ClinVar as Benign. ClinVar VariationId is 130596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0105 (1594/152222) while in subpopulation AFR AF = 0.0363 (1508/41528). AF 95% confidence interval is 0.0348. There are 21 homozygotes in GnomAd4. There are 764 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXYLT1	NM_014254.3 link	c.469G>A	p.Val157Ile	missense_variant	Exon 4 of 6	ENST00000261234.11	NP_055069.1	Q9Y2B1
RXYLT1	XM_047428078.1 link	c.160G>A	p.Val54Ile	missense_variant	Exon 3 of 5		XP_047284034.1
RXYLT1	NM_001278237.2 link	c.-312G>A		5_prime_UTR_variant	Exon 4 of 6		NP_001265166.1	Q9Y2B1
RXYLT1	XM_047428079.1 link	c.*18G>A		3_prime_UTR_variant	Exon 5 of 5		XP_047284035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXYLT1	ENST00000261234.11 link	c.469G>A	p.Val157Ile	missense_variant	Exon 4 of 6	1	NM_014254.3	ENSP00000261234.6		Q9Y2B1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1591

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00267

AC:

667

AN:

249602

AF XY:

0.00206

show subpopulations

Gnomad AFR exome

AF:

0.0357

Gnomad AMR exome

AF:

0.00152

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00108

AC:

1576

AN:

1459870

Hom.:

Cov.:

AF XY:

0.000959

AC XY:

696

AN XY:

726042

show subpopulations

African (AFR)

AF:

0.0358

AC:

1194

AN:

33344

American (AMR)

AF:

0.00200

AC:

AN:

44420

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26036

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39644

South Asian (SAS)

AF:

0.000151

AC:

AN:

85852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00278

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.000116

AC:

129

AN:

1111142

Other (OTH)

AF:

0.00217

AC:

131

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

150

225

300

375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0105

AC:

1594

AN:

152222

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

764

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0363

AC:

1508

AN:

41528

American (AMR)

AF:

0.00373

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68024

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

149

223

298

372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00339

Hom.:

Bravo

AF:

0.0120

ESP6500AA

AF:

0.0390

AC:

172

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00343

AC:

416

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000601

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jan 13, 2020

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Jun 16, 2016

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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.099

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.0044

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.0

PhyloP100

0.13

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.47

REVEL

Benign

0.034

Sift

Benign

0.55

Sift4G

Benign

0.23

Polyphen

0.0070

Vest4

0.077

MVP

0.014

MPC

0.13

ClinPred

0.00051

GERP RS

-0.052

Varity_R

0.0086

gMVP

0.18

Mutation Taster

=299/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over