rs146732392

chr12-63802265-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014254.3(RXYLT1):c.603C>T(p.Leu201=) 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:4
• Conservation: PhyloP100: 0.412

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 283541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-63802265-C-T is described in Lovd as [Likely_benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXYLT1	NM_014254.3	c.603C>T	p.Leu201=	synonymous_variant	4/6	ENST00000261234.11
RXYLT1	XM_047428078.1	c.294C>T	p.Leu98=	synonymous_variant	3/5
RXYLT1	NM_001278237.2	c.-178C>T		5_prime_UTR_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXYLT1	ENST00000261234.11	c.603C>T	p.Leu201=	synonymous_variant	4/6	1	NM_014254.3	P1

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

GnomAD3 exomes AF: 0.00715 AC: 1796 AN: 251214 Hom.: 51 AF XY: 0.00904 AC XY: 1227 AN XY: 135754

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 SAS exome AF: 0.0521

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

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0500

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.00128

Gnomad4 OTH exome AF: 0.00450

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

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0564

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00140

Gnomad4 OTH AF: 0.00142

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 30, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 22, 2020	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 18, 2016	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:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	5.1
Dann	Benign	0.78

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

Other links and lift over

dbSNP: rs146732392; hg19: chr12-64196045;