rs61935924

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_StrongBA1

The NM_014254.3(RXYLT1):c.67G>A(p.Ala23Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0968 in 1,609,046 control chromosomes in the GnomAD database, including 8,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A23A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.076 ( 589 hom., cov: 32)

Exomes 𝑓: 0.099 ( 7673 hom. )

Consequence

RXYLT1
NM_014254.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.05

Publications

16 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: PanelApp Australia, Genomics England PanelApp, G2P
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RXYLT1 links:

ENSG00000249753 (HGNC:):

ENSG00000249753 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=0.0017903745).

BP6

Variant 12-63780027-G-A is Benign according to our data. Variant chr12-63780027-G-A is described in ClinVar as Benign. ClinVar VariationId is 130597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014254.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXYLT1	NM_014254.3	MANE Select	c.67G>A	p.Ala23Thr	missense	Exon 1 of 6	NP_055069.1	Q9Y2B1
	RXYLT1	NM_001278237.2		c.-1047G>A		5_prime_UTR	Exon 1 of 6	NP_001265166.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RXYLT1	ENST00000261234.11	TSL:1 MANE Select	c.67G>A	p.Ala23Thr	missense	Exon 1 of 6	ENSP00000261234.6	Q9Y2B1
RXYLT1	ENST00000536219.5	TSL:1	n.186G>A		non_coding_transcript_exon	Exon 1 of 3
RXYLT1	ENST00000947510.1		c.67G>A	p.Ala23Thr	missense	Exon 1 of 6	ENSP00000617569.1

Frequencies

GnomAD3 genomes

AF:

0.0765

AC:

11628

AN:

152028

Hom.:

590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0512

Gnomad ASJ

AF:

0.0793

Gnomad EAS

AF:

0.0112

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.179

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.0757

GnomAD2 exomes

AF:

0.0866

AC:

21260

AN:

245612

AF XY:

0.0912

show subpopulations

Gnomad AFR exome

AF:

0.0242

Gnomad AMR exome

AF:

0.0418

Gnomad ASJ exome

AF:

0.0828

Gnomad EAS exome

AF:

0.0120

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.0982

GnomAD4 exome

AF:

0.0989

AC:

144161

AN:

1456910

Hom.:

7673

Cov.:

AF XY:

0.100

AC XY:

72657

AN XY:

725056

show subpopulations

African (AFR)

AF:

0.0235

AC:

771

AN:

32826

American (AMR)

AF:

0.0446

AC:

1987

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.0855

AC:

2223

AN:

26010

East Asian (EAS)

AF:

0.0104

AC:

410

AN:

39358

South Asian (SAS)

AF:

0.106

AC:

9177

AN:

86180

European-Finnish (FIN)

AF:

0.122

AC:

6279

AN:

51632

Middle Eastern (MID)

AF:

0.124

AC:

714

AN:

5746

European-Non Finnish (NFE)

AF:

0.105

AC:

116965

AN:

1110438

Other (OTH)

AF:

0.0936

AC:

5635

AN:

60190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

7691

15381

23072

30762

38453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4074

8148

12222

16296

20370

<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:

0.0764

AC:

11626

AN:

152136

Hom.:

589

Cov.:

AF XY:

0.0766

AC XY:

5694

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0244

AC:

1015

AN:

41556

American (AMR)

AF:

0.0511

AC:

782

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0793

AC:

275

AN:

3468

East Asian (EAS)

AF:

0.0115

AC:

AN:

5152

South Asian (SAS)

AF:

0.105

AC:

506

AN:

4824

European-Finnish (FIN)

AF:

0.122

AC:

1288

AN:

10600

Middle Eastern (MID)

AF:

0.172

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.109

AC:

7388

AN:

67936

Other (OTH)

AF:

0.0758

AC:

160

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

531

1063

1594

2126

2657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0972

Hom.:

2637

Bravo

AF:

0.0672

TwinsUK

AF:

0.0955

AC:

354

ALSPAC

AF:

0.0989

AC:

381

ESP6500AA

AF:

0.0284

AC:

125

ESP6500EA

AF:

0.105

AC:

903

ExAC

AF:

0.0883

AC:

10721

Asia WGS

AF:

0.0550

AC:

190

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0048

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.2

PhyloP100

5.1

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.43

REVEL

Benign

0.089

Sift

Benign

0.28

Sift4G

Benign

0.49

Polyphen

1.0

Vest4

0.22

MPC

2.3

ClinPred

0.023

GERP RS

2.5

PromoterAI

-0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.092

gMVP

0.70

Mutation Taster

=82/18

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over