12-63779870-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000536219.5(RXYLT1):n.29G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,570,228 control chromosomes in the GnomAD database, including 1,297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.042 (395 hom., cov: 32)
  • Exomes 𝑓: 0.012 (902 hom.)
• Consequence: RXYLT1 ENST00000536219.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.56

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-63779870-G-A is Benign according to our data. Variant chr12-63779870-G-A is described in ClinVar as [Benign]. Clinvar id is 672804.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXYLT1	NM_014254.3			upstream_gene_variant		ENST00000261234.11
RXYLT1	NM_001278237.2			upstream_gene_variant
RXYLT1	XM_047428079.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000509615.2	n.238+15611C>T		intron_variant, non_coding_transcript_variant		5
RXYLT1	ENST00000261234.11			upstream_gene_variant		1	NM_014254.3	P1

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6447 AN: 152130 Hom.: 399 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0877

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.0117 AC: 16574 AN: 1417990 Hom.: 902 Cov.: 28 AF XY: 0.0129 AC XY: 9115 AN XY: 705674

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.00769

Gnomad4 ASJ exome AF: 0.00123

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.0728

Gnomad4 FIN exome AF: 0.0000254

Gnomad4 NFE exome AF: 0.000401

Gnomad4 OTH exome AF: 0.0233

GnomAD4 genome AF: 0.0423 AC: 6444 AN: 152238 Hom.: 395 Cov.: 32 AF XY: 0.0429 AC XY: 3191 AN XY: 74430

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.0871

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.0340

Alfa AF: 0.00192 Hom.: 4

Bravo AF: 0.0456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.0
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs75517044; hg19: chr12-64173650;