NM_014254.3:c.603C>T

Variant names:

• chr12-63802265-C-T
• rs146732392
• NM_014254.3:c.603C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014254.3(RXYLT1):​c.603C>T​(p.Leu201Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 1,614,028 control chromosomes in the GnomAD database, including 165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (11 hom., cov: 31)
  • Exomes 𝑓: 0.0042 (154 hom.)
• Consequence: RXYLT1 NM_014254.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.412
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 12-63802265-C-T is Benign according to our data. Variant chr12-63802265-C-T is described in ClinVar as Benign. ClinVar VariationId is 283541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.412 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0509 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.603C>T	p.Leu201Leu	synonymous	Exon 4 of 6	NP_055069.1
	RXYLT1	NM_001278237.2		c.-178C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 6	NP_001265166.1
	RXYLT1	NM_001278237.2		c.-178C>T		5_prime_UTR	Exon 4 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.603C>T	p.Leu201Leu	synonymous	Exon 4 of 6	ENSP00000261234.6
	RXYLT1	ENST00000537373.6	TSL:1	n.*338C>T		non_coding_transcript_exon	Exon 4 of 6	ENSP00000440280.2
	RXYLT1	ENST00000537373.6	TSL:1	n.*338C>T		3_prime_UTR	Exon 4 of 6	ENSP00000440280.2

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 384 AN: 152140 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00715 AC: 1796 AN: 251214 AF XY: 0.00904

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00137

Gnomad OTH exome AF: 0.00441

GnomAD4 exome AF: 0.00415 AC: 6072 AN: 1461770 Hom.: 154 Cov.: 31 AF XY: 0.00554 AC XY: 4028 AN XY: 727168

African (AFR) AF: 0.000418 AC: 14 AN: 33480

American (AMR) AF: 0.000335 AC: 15 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39680

South Asian (SAS) AF: 0.0500 AC: 4313 AN: 86242

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53400

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5764

European-Non Finnish (NFE) AF: 0.00128 AC: 1419 AN: 1111980

Other (OTH) AF: 0.00450 AC: 272 AN: 60382

GnomAD4 genome AF: 0.00252 AC: 383 AN: 152258 Hom.: 11 Cov.: 31 AF XY: 0.00318 AC XY: 237 AN XY: 74444

African (AFR) AF: 0.000168 AC: 7 AN: 41554

American (AMR) AF: 0.000131 AC: 2 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0564 AC: 272 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00140 AC: 95 AN: 68016

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00123 Hom.: 1

Bravo AF: 0.00105

Asia WGS AF: 0.0240 AC: 84 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Sep 30, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Dec 22, 2020

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

May 18, 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 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.1
DANN	Benign	0.78
PhyloP100		0.41
Mutation Taster		=282/18	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: rs146732392; hg19: chr12-64196045;