rs536862073

Variant names:

• chr12-63809032-G-A
• rs536862073
• NM_014254.3:c.1272G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-63809032-G-A
• chr12-63809032-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_014254.3(RXYLT1):​c.1272G>A​(p.Glu424Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,582,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: RXYLT1 NM_014254.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.28
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 12-63809032-G-A is Benign according to our data. Variant chr12-63809032-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 473412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.28 with no splicing effect.

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.1272G>A	p.Glu424Glu	synonymous	Exon 6 of 6	NP_055069.1
	RXYLT1	NM_001278237.2		c.492G>A	p.Glu164Glu	synonymous	Exon 6 of 6	NP_001265166.1
	RXYLT1-AS1	NR_126167.1		n.468-92C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXYLT1	ENST00000261234.11	TSL:1 MANE Select	c.1272G>A	p.Glu424Glu	synonymous	Exon 6 of 6	ENSP00000261234.6
	RXYLT1	ENST00000537373.6	TSL:1	n.*1007G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000440280.2
	RXYLT1	ENST00000537373.6	TSL:1	n.*1007G>A		3_prime_UTR	Exon 6 of 6	ENSP00000440280.2

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000762 AC: 17 AN: 223174 AF XY: 0.0000902

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.000186

GnomAD4 exome AF: 0.000106 AC: 151 AN: 1430812 Hom.: 0 Cov.: 29 AF XY: 0.000107 AC XY: 76 AN XY: 711754

African (AFR) AF: 0.00 AC: 0 AN: 31396

American (AMR) AF: 0.00 AC: 0 AN: 36084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39542

South Asian (SAS) AF: 0.00 AC: 0 AN: 80170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 0.000134 AC: 148 AN: 1100696

Other (OTH) AF: 0.0000507 AC: 3 AN: 59218

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000251 Hom.: 0

Bravo AF: 0.000110

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	RXYLT1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	3.6
DANN	Benign	0.58
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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: rs536862073; hg19: chr12-64202812;