chr12-63804938-T-G

Position:

• chr12-63804938-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014254.3(RXYLT1):​c.744-296T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 249,666 control chromosomes in the GnomAD database, including 215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (110 hom., cov: 32)
  • Exomes 𝑓: 0.040 (105 hom.)
• Consequence: RXYLT1 NM_014254.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.616

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-63804938-T-G is Benign according to our data. Variant chr12-63804938-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1215189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXYLT1	NM_014254.3	c.744-296T>G		intron_variant		ENST00000261234.11
RXYLT1	NM_001278237.2	c.-37-296T>G		intron_variant
RXYLT1	XM_047428078.1	c.435-296T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXYLT1	ENST00000261234.11	c.744-296T>G		intron_variant		1	NM_014254.3	P1

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4958 AN: 152176 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.00789

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0468

Gnomad OTH AF: 0.0387

GnomAD4 exome AF: 0.0399 AC: 3890 AN: 97372 Hom.: 105 Cov.: 0 AF XY: 0.0405 AC XY: 2025 AN XY: 50012

Gnomad4 AFR exome AF: 0.00735

Gnomad4 AMR exome AF: 0.0349

Gnomad4 ASJ exome AF: 0.0552

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0153

Gnomad4 FIN exome AF: 0.0409

Gnomad4 NFE exome AF: 0.0464

Gnomad4 OTH exome AF: 0.0378

GnomAD4 genome AF: 0.0325 AC: 4954 AN: 152294 Hom.: 110 Cov.: 32 AF XY: 0.0313 AC XY: 2334 AN XY: 74472

Gnomad4 AFR AF: 0.00787

Gnomad4 AMR AF: 0.0398

Gnomad4 ASJ AF: 0.0597

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.0391

Gnomad4 NFE AF: 0.0468

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0389 Hom.: 17

Bravo AF: 0.0326

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.48

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: rs78691954; hg19: chr12-64198718;