ENST00000537373.6:n.*1085C>G

Variant names:

• chr12-63809110-C-G
• rs1876465
• ENST00000537373.6:n.*1085C>G

Variant summary

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

The ENST00000537373.6(RXYLT1):​n.*1085C>G 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 0.104 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 ENST00000537373.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0840
• Publications: 7 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-AS1 (HGNC:48910): (RXYLT1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 198206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000537373.6. 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.*18C>G		3_prime_UTR	Exon 6 of 6	NP_055069.1
	RXYLT1	NM_001278237.2		c.*18C>G		3_prime_UTR	Exon 6 of 6	NP_001265166.1
	RXYLT1-AS1	NR_126167.1		n.468-170G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXYLT1	ENST00000537373.6	TSL:1	n.*1085C>G		non_coding_transcript_exon	Exon 6 of 6	ENSP00000440280.2
	RXYLT1	ENST00000261234.11	TSL:1 MANE Select	c.*18C>G		3_prime_UTR	Exon 6 of 6	ENSP00000261234.6
	RXYLT1	ENST00000537373.6	TSL:1	n.*1085C>G		3_prime_UTR	Exon 6 of 6	ENSP00000440280.2

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

GnomAD2 exomes AF: 0.120 AC: 19139 AN: 159986 AF XY: 0.111

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 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

African (AFR) AF: 0.229 AC: 6253 AN: 27320

American (AMR) AF: 0.178 AC: 5222 AN: 29400

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3133 AN: 22894

East Asian (EAS) AF: 0.230 AC: 8384 AN: 36458

South Asian (SAS) AF: 0.0757 AC: 5570 AN: 73618

European-Finnish (FIN) AF: 0.0727 AC: 3054 AN: 42000

Middle Eastern (MID) AF: 0.119 AC: 483 AN: 4052

European-Non Finnish (NFE) AF: 0.0909 AC: 91836 AN: 1010500

Other (OTH) AF: 0.109 AC: 5916 AN: 54228

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

African (AFR) AF: 0.235 AC: 9764 AN: 41478

American (AMR) AF: 0.168 AC: 2562 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3472

East Asian (EAS) AF: 0.184 AC: 952 AN: 5176

South Asian (SAS) AF: 0.0806 AC: 389 AN: 4826

European-Finnish (FIN) AF: 0.0662 AC: 700 AN: 10578

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0958 AC: 6513 AN: 67994

Other (OTH) AF: 0.134 AC: 282 AN: 2112

Alfa AF: 0.121 Hom.: 241

Bravo AF: 0.157

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.72
PhyloP100		0.084
Mutation Taster		=100/0	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: rs1876465; hg19: chr12-64202890;