3-195270644-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152531.5(XXYLT1):c.415C>T(p.Leu139Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,413,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: XXYLT1 NM_152531.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.18

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35439447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XXYLT1	NM_152531.5	c.415C>T	p.Leu139Phe	missense_variant	1/4	ENST00000310380.11
XXYLT1	XM_017005749.3	c.415C>T	p.Leu139Phe	missense_variant	1/4
XXYLT1	XR_924105.4	n.516C>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XXYLT1	ENST00000310380.11	c.415C>T	p.Leu139Phe	missense_variant	1/4	1	NM_152531.5	P1
XXYLT1	ENST00000455281.1	c.220C>T	p.Leu74Phe	missense_variant, NMD_transcript_variant	1/3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1413604 Hom.: 0 Cov.: 34 AF XY: 0.00000142 AC XY: 1 AN XY: 703018

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.415C>T (p.L139F) alteration is located in exon 1 (coding exon 1) of the XXYLT1 gene. This alteration results from a C to T substitution at nucleotide position 415, causing the leucine (L) at amino acid position 139 to be replaced by a phenylalanine (F). 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	0.22
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0029	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.16
Sift	Benign	0.34	T
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.46
MutPred		0.67		Loss of disorder (P = 0.2083);
MVP		0.15
MPC		0.64
ClinPred		0.89	D
GERP RS		3.8
Varity_R		0.32
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-194991373; COSMIC: COSV58751064; COSMIC: COSV58751064;