12-63802131-G-T

Position:

• chr12-63802131-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014254.3(RXYLT1):​c.469G>T​(p.Val157Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RXYLT1 NM_014254.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09740013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXYLT1	NM_014254.3	c.469G>T	p.Val157Phe	missense_variant	4/6	ENST00000261234.11	NP_055069.1
RXYLT1	XM_047428078.1	c.160G>T	p.Val54Phe	missense_variant	3/5		XP_047284034.1
RXYLT1	NM_001278237.2	c.-312G>T		5_prime_UTR_variant	4/6		NP_001265166.1
RXYLT1	XM_047428079.1	c.*18G>T		3_prime_UTR_variant	5/5		XP_047284035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXYLT1	ENST00000261234.11	c.469G>T	p.Val157Phe	missense_variant	4/6	1	NM_014254.3	ENSP00000261234.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.2
DANN	Benign	0.94
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.056
Sift	Benign	0.54	T
Sift4G	Benign	0.12	T
Polyphen		0.90	P
Vest4		0.23
MutPred		0.28		Gain of catalytic residue at N161 (P = 0);
MVP		0.085
MPC		0.53
ClinPred		0.28	T
GERP RS		-0.052
Varity_R		0.036
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs114036100; hg19: chr12-64195911;