Variant 3-195270709-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152531.5(XXYLT1):c.350A>C(p.Lys117Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000157 in 1,590,280 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

XXYLT1
NM_152531.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
XXYLT1	NM_152531.5 linkuse as main transcript	c.350A>C	p.Lys117Thr	missense_variant	1/4	ENST00000310380.11
XXYLT1	XM_017005749.3 linkuse as main transcript	c.350A>C	p.Lys117Thr	missense_variant	1/4
XXYLT1	XR_924105.4 linkuse as main transcript	n.451A>C		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XXYLT1	ENST00000310380.11 linkuse as main transcript	c.350A>C	p.Lys117Thr	missense_variant	1/4	1	NM_152531.5	P1	Q8NBI6-1
XXYLT1	ENST00000455281.1 linkuse as main transcript	c.155A>C	p.Lys52Thr	missense_variant, NMD_transcript_variant	1/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

209166

Hom.:

AF XY:

0.0000341

AC XY:

AN XY:

117196

show subpopulations

Gnomad AFR exome

AF:

0.000206

Gnomad AMR exome

AF:

0.0000962

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000904

AC:

AN:

1438116

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

715534

show subpopulations

Gnomad4 AFR exome

AF:

0.000260

Gnomad4 AMR exome

AF:

0.0000936

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.000170

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

Jul 15, 2021

The c.350A>C (p.K117T) alteration is located in exon 1 (coding exon 1) of the XXYLT1 gene. This alteration results from a A to C substitution at nucleotide position 350, causing the lysine (K) at amino acid position 117 to be replaced by a threonine (T). 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

Pathogenic

0.89

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.21

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.67

M_CAP

Pathogenic

0.31

MetaRNN

Uncertain

0.69

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.19

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.016

Polyphen

0.87

Vest4

0.56

MutPred

0.53

Loss of MoRF binding (P = 0.0502);

MVP

0.75

MPC

1.3

ClinPred

0.83

GERP RS

3.5

Varity_R

0.49

gMVP

0.75

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