12-63809110-C-G

Position:

• chr12-63809110-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014254.3(RXYLT1):​c.*18C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,452,590 control chromosomes in the GnomAD database, including 9,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1881 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7475 hom.)
• Consequence: RXYLT1 NM_014254.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0840

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-AS1 (HGNC:48910): (RXYLT1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-63809110-C-G is Benign according to our data. Variant chr12-63809110-C-G is described in ClinVar as [Benign]. Clinvar id is 198206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-63809110-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXYLT1	NM_014254.3	c.*18C>G		3_prime_UTR_variant	6/6	ENST00000261234.11	NP_055069.1
RXYLT1-AS1	NR_126167.1	n.468-170G>C		intron_variant, non_coding_transcript_variant
RXYLT1	NM_001278237.2	c.*18C>G		3_prime_UTR_variant	6/6		NP_001265166.1
RXYLT1	XM_047428078.1	c.*18C>G		3_prime_UTR_variant	5/5		XP_047284034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXYLT1	ENST00000261234.11	c.*18C>G		3_prime_UTR_variant	6/6	1	NM_014254.3	ENSP00000261234	P1
RXYLT1-AS1	ENST00000546214.1	n.468-170G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21640 AN: 152002 Hom.: 1850 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.133

GnomAD3 exomes AF: 0.120 AC: 19139 AN: 159986 Hom.: 1322 AF XY: 0.111 AC XY: 9932 AN XY: 89108

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.180

Gnomad SAS exome AF: 0.0735

Gnomad FIN exome AF: 0.0710

Gnomad NFE exome AF: 0.0965

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.0998 AC: 129851 AN: 1300470 Hom.: 7475 Cov.: 22 AF XY: 0.0989 AC XY: 64293 AN XY: 649908

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.0757

Gnomad4 FIN exome AF: 0.0727

Gnomad4 NFE exome AF: 0.0909

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.143 AC: 21733 AN: 152120 Hom.: 1881 Cov.: 32 AF XY: 0.142 AC XY: 10586 AN XY: 74376

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.0662

Gnomad4 NFE AF: 0.0958

Gnomad4 OTH AF: 0.134

Alfa AF: 0.121 Hom.: 241

Bravo AF: 0.157

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 08, 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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 26, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.72

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: rs1876465; hg19: chr12-64202890;