rs1555225967

Variant names:

• chr12-63781095-A-C
• rs1555225967
• NM_014254.3:c.246A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-63781095-A-C
• chr12-63781095-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014254.3(RXYLT1):​c.246A>C​(p.Lys82Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RXYLT1 NM_014254.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53
• 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 Gene-Disease associations (from GenCC):

• muscle-eye-brain disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, G2P
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000249753 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14218637).

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.246A>C	p.Lys82Asn	missense	Exon 2 of 6	NP_055069.1	Q9Y2B1
	RXYLT1	NM_001278237.2		c.-535A>C		5_prime_UTR	Exon 2 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.246A>C	p.Lys82Asn	missense	Exon 2 of 6	ENSP00000261234.6	Q9Y2B1
	RXYLT1	ENST00000536219.5	TSL:1	n.365A>C		non_coding_transcript_exon	Exon 2 of 3
	RXYLT1	ENST00000537373.6	TSL:1	n.128A>C		non_coding_transcript_exon	Exon 2 of 6	ENSP00000440280.2	G3V1K2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.5
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.049
Sift	Benign	0.036	D
Sift4G	Benign	0.40	T
Polyphen		0.36	B
Vest4		0.33
MutPred		0.36		Loss of ubiquitination at K82 (P = 0.003)
MVP		0.092
MPC		0.62
ClinPred		0.76	D
GERP RS		3.1
Varity_R		0.12
gMVP		0.31
Mutation Taster		=80/20	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: rs1555225967; hg19: chr12-64174875;