Variant 3-195069986-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152531.5(XXYLT1):c.911C>T(p.Pro304Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,608,976 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

XXYLT1
NM_152531.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

Variant links:

Genes affected

XXYLT1 (HGNC:26639): (xyloside xylosyltransferase 1) Enables magnesium ion binding activity; manganese ion binding activity; and xylosyl alpha-1,3-xylosyltransferase activity. Involved in O-glycan processing. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

XXYLT1 links:

XXYLT1 (HGNC:):

XXYLT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0439834).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XXYLT1	NM_152531.5 linkuse as main transcript	c.911C>T	p.Pro304Leu	missense_variant	4/4	ENST00000310380.11	NP_689744.3	Q8NBI6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XXYLT1	ENST00000310380.11 linkuse as main transcript	c.911C>T	p.Pro304Leu	missense_variant	4/4	1	NM_152531.5	ENSP00000309640.6		Q8NBI6-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000115

AC:

AN:

243728

Hom.:

AF XY:

0.000135

AC XY:

AN XY:

133018

show subpopulations

Gnomad AFR exome

AF:

0.0000658

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000561

Gnomad SAS exome

AF:

0.000491

Gnomad FIN exome

AF:

0.0000547

Gnomad NFE exome

AF:

0.0000897

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000171

AC:

249

AN:

1456650

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

130

AN XY:

724890

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.0000412

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000105

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000121

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.000133

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 08, 2024

The c.911C>T (p.P304L) alteration is located in exon 4 (coding exon 4) of the XXYLT1 gene. This alteration results from a C to T substitution at nucleotide position 911, causing the proline (P) at amino acid position 304 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.054

T;.;T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.78

T;T;T;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.044

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.029

Sift

Benign

0.34

T;T;T;T

Sift4G

Benign

0.33

T;T;T;T

Polyphen

0.0080

B;B;.;B

Vest4

0.049

MVP

0.067

MPC

0.50

ClinPred

0.028

GERP RS

3.0

Varity_R

0.027

gMVP

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over