rs115076664

Variant names:

• chr12-63805315-G-A
• rs115076664
• NM_014254.3:c.825G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_014254.3(RXYLT1):​c.825G>A​(p.Thr275Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000442 in 1,613,318 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: RXYLT1 NM_014254.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.00
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-63805315-G-A is Benign according to our data. Variant chr12-63805315-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 386581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00248 (378/152276) while in subpopulation AFR AF = 0.00883 (367/41570). AF 95% confidence interval is 0.00808. There are 1 homozygotes in GnomAd4. There are 164 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXYLT1	NM_014254.3	MANE Select	c.825G>A	p.Thr275Thr	synonymous	Exon 5 of 6	NP_055069.1	Q9Y2B1
	RXYLT1	NM_001278237.2		c.45G>A	p.Thr15Thr	synonymous	Exon 5 of 6	NP_001265166.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXYLT1	ENST00000261234.11	TSL:1 MANE Select	c.825G>A	p.Thr275Thr	synonymous	Exon 5 of 6	ENSP00000261234.6	Q9Y2B1
	RXYLT1	ENST00000537373.6	TSL:1	n.*560G>A		non_coding_transcript_exon	Exon 5 of 6	ENSP00000440280.2	G3V1K2
	RXYLT1	ENST00000537373.6	TSL:1	n.*560G>A		3_prime_UTR	Exon 5 of 6	ENSP00000440280.2	G3V1K2

Frequencies

GnomAD3 genomes AF: 0.00247 AC: 376 AN: 152160 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00881

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

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: 0.0000147

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000591 AC: 148 AN: 250428 AF XY: 0.000451

Gnomad AFR exome AF: 0.00870

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000229 AC: 335 AN: 1461042 Hom.: 0 Cov.: 30 AF XY: 0.000201 AC XY: 146 AN XY: 726814

African (AFR) AF: 0.00856 AC: 286 AN: 33428

American (AMR) AF: 0.000247 AC: 11 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111664

Other (OTH) AF: 0.000365 AC: 22 AN: 60356

GnomAD4 genome AF: 0.00248 AC: 378 AN: 152276 Hom.: 1 Cov.: 32 AF XY: 0.00220 AC XY: 164 AN XY: 74468

African (AFR) AF: 0.00883 AC: 367 AN: 41570

American (AMR) AF: 0.000523 AC: 8 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00109 Hom.: 0

Bravo AF: 0.00286

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.13
DANN	Benign	0.79
PhyloP100		-3.0
Mutation Taster		=99/1	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: rs115076664; hg19: chr12-64199095; COSMIC: COSV99706891; COSMIC: COSV99706891;