NM_014254.3:c.67G>A

Variant names:

• chr12-63780027-G-A
• rs61935924
• NM_014254.3:c.67G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 5.05
• Publications: 16 publications found

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

ENSG00000249753 (HGNC:):

ACMG classification

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

Selected	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
	RXYLT1	NM_001278237.2		c.-1047G>A		5_prime_UTR	Exon 1 of 6	NP_001265166.1

Ensembl Transcripts

Selected	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
	RXYLT1	ENST00000536219.5	TSL:1	n.186G>A		non_coding_transcript_exon	Exon 1 of 3
	RXYLT1	ENST00000543342.5	TSL:5	n.67G>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000440845.1

Frequencies

GnomAD3 genomes AF: 0.0765 AC: 11628 AN: 152028 Hom.: 590 Cov.: 32

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

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.: 32 AF XY: 0.100 AC XY: 72657 AN XY: 725056

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

GnomAD4 genome AF: 0.0764 AC: 11626 AN: 152136 Hom.: 589 Cov.: 32 AF XY: 0.0766 AC XY: 5694 AN XY: 74370

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: 59 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: 50 AN: 290

European-Non Finnish (NFE) AF: 0.109 AC: 7388 AN: 67936

Other (OTH) AF: 0.0758 AC: 160 AN: 2110

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

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Jan 30, 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.

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0048	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.2	T
PhyloP100		5.1
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.089
Sift	Benign	0.28	T
Sift4G	Benign	0.49	T
Polyphen		1.0	D
Vest4		0.22
MPC		2.3
ClinPred		0.023	T
GERP RS		2.5
PromoterAI		-0.031	Neutral
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)

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

Other links and lift over

dbSNP: rs61935924; hg19: chr12-64173807; COSMIC: COSV54170288; COSMIC: COSV54170288;