12-42144518-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_173601.2(GXYLT1):c.129C>T(p.Ala43=) variant causes a synonymous change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.027 (139 hom.)
  • Failed GnomAD Quality Control
• Consequence: GXYLT1 NM_173601.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.86

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 12-42144518-G-A is Benign according to our data. Variant chr12-42144518-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642894.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GXYLT1	NM_173601.2	c.129C>T	p.Ala43=	synonymous_variant	1/8	ENST00000398675.8
GXYLT1	NM_001099650.2	c.129C>T	p.Ala43=	synonymous_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GXYLT1	ENST00000398675.8	c.129C>T	p.Ala43=	synonymous_variant	1/8	1	NM_173601.2	P4
GXYLT1	ENST00000280876.6	c.129C>T	p.Ala43=	synonymous_variant	1/7	1		A1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 649 AN: 98828 Hom.: 0 Cov.: 34 FAILED QC

Gnomad AFR AF: 0.00719

Gnomad AMI AF: 0.0119

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00405

Gnomad EAS AF: 0.00606

Gnomad SAS AF: 0.00824

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00607

Gnomad OTH AF: 0.00347

GnomAD3 exomes AF: 0.0000418 AC: 3 AN: 71814 Hom.: 0 AF XY: 0.0000716 AC XY: 3 AN XY: 41884

Gnomad AFR exome AF: 0.00113

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: 0.0000756

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0269 AC: 30146 AN: 1120762 Hom.: 139 Cov.: 32 AF XY: 0.0323 AC XY: 17549 AN XY: 542504

Gnomad4 AFR exome AF: 0.0192

Gnomad4 AMR exome AF: 0.0804

Gnomad4 ASJ exome AF: 0.0489

Gnomad4 EAS exome AF: 0.0384

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.0699

Gnomad4 NFE exome AF: 0.0178

Gnomad4 OTH exome AF: 0.0361

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00656 AC: 649 AN: 98862 Hom.: 0 Cov.: 34 AF XY: 0.00731 AC XY: 353 AN XY: 48292

Gnomad4 AFR AF: 0.00718

Gnomad4 AMR AF: 0.00496

Gnomad4 ASJ AF: 0.00405

Gnomad4 EAS AF: 0.00608

Gnomad4 SAS AF: 0.00823

Gnomad4 FIN AF: 0.0103

Gnomad4 NFE AF: 0.00608

Gnomad4 OTH AF: 0.00343

Alfa AF: 0.340 Hom.: 0

Asia WGS AF: 0.000593 AC: 2 AN: 3384

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

Aug 01, 2023

GXYLT1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	16
Dann	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

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: rs112525075; hg19: chr12-42538320; COSMIC: COSV55135896;