12-42119003-G-T

Position:

• chr12-42119003-G-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_173601.2(GXYLT1):​c.483C>A​(p.Gly161=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GXYLT1 NM_173601.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0850

Genes affected

GXYLT1 (HGNC:27482): (glucoside xylosyltransferase 1) GXYLT1 is a xylosyltransferase (EC 2.4.2.-) that adds the first xylose to O-glucose-modified residues in the epidermal growth factor (EGF; MIM 131530) repeats of proteins such as NOTCH1 (MIM 190198) (Sethi et al., 2010 [PubMed 19940119]).[supplied by OMIM, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 12-42119003-G-T is Benign according to our data. Variant chr12-42119003-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.085 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GXYLT1	NM_173601.2	c.483C>A	p.Gly161=	synonymous_variant	3/8	ENST00000398675.8
GXYLT1	NM_001099650.2	c.390C>A	p.Gly130=	synonymous_variant	2/7
GXYLT1	XM_017019211.1	c.138C>A	p.Gly46=	synonymous_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GXYLT1	ENST00000398675.8	c.483C>A	p.Gly161=	synonymous_variant	3/8	1	NM_173601.2	P4
GXYLT1	ENST00000280876.6	c.390C>A	p.Gly130=	synonymous_variant	2/7	1		A1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 23 AN: 127342 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000234

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000493

Gnomad FIN AF: 0.000602

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000157

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00595 AC: 7442 AN: 1249866 Hom.: 0 Cov.: 32 AF XY: 0.00816 AC XY: 5000 AN XY: 612394

Gnomad4 AFR exome AF: 0.00359

Gnomad4 AMR exome AF: 0.00927

Gnomad4 ASJ exome AF: 0.0151

Gnomad4 EAS exome AF: 0.00395

Gnomad4 SAS exome AF: 0.0145

Gnomad4 FIN exome AF: 0.0248

Gnomad4 NFE exome AF: 0.00463

Gnomad4 OTH exome AF: 0.00480

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000180 AC: 23 AN: 127452 Hom.: 0 Cov.: 32 AF XY: 0.000243 AC XY: 15 AN XY: 61842

Gnomad4 AFR AF: 0.000115

Gnomad4 AMR AF: 0.000234

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000493

Gnomad4 FIN AF: 0.000602

Gnomad4 NFE AF: 0.000157

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0346 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

GXYLT1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.4
DANN	Benign	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: rs775422274; hg19: chr12-42512805; COSMIC: COSV55135121;