chr12-63780030-G-A

Position:

• chr12-63780030-G-A

Variant summary

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

The NM_014254.3(RXYLT1):​c.70G>A​(p.Ala24Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,456,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A24P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: RXYLT1 NM_014254.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.05

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]

(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=0.2633751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXYLT1	NM_014254.3	c.70G>A	p.Ala24Thr	missense_variant	1/6	ENST00000261234.11
RXYLT1	XM_047428079.1	c.70G>A	p.Ala24Thr	missense_variant	1/5
RXYLT1	NM_001278237.2	c.-1044G>A		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXYLT1	ENST00000261234.11	c.70G>A	p.Ala24Thr	missense_variant	1/6	1	NM_014254.3	P1
	ENST00000509615.2	n.238+15451C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000815 AC: 2 AN: 245386 Hom.: 0 AF XY: 0.00000751 AC XY: 1 AN XY: 133234

Gnomad AFR exome AF: 0.0000654

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000900

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1456164 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724712

Gnomad4 AFR exome AF: 0.0000305

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000763

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000194

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.10
Sift	Benign	0.19	T
Sift4G	Benign	0.28	T
Polyphen		0.45	B
Vest4		0.53
MVP		0.048
MPC		2.2
ClinPred		0.77	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.076
gMVP		0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs377034865; hg19: chr12-64173810;