NM_022167.4:c.8C>T

Variant names:

• chr17-50346148-C-T
• rs1186744711
• NM_022167.4:c.8C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022167.4(XYLT2):​c.8C>T​(p.Ala3Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000171 in 1,109,502 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: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: XYLT2 NM_022167.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53
• Publications: 0 publications found

Genes affected

XYLT2 (HGNC:15517): (xylosyltransferase 2) The protein encoded by this gene is an isoform of xylosyltransferase, which belongs to a family of glycosyltransferases. This enzyme transfers xylose from UDP-xylose to specific serine residues of the core protein and initiates the biosynthesis of glycosaminoglycan chains in proteoglycans including chondroitin sulfate, heparan sulfate, heparin and dermatan sulfate. The enzyme activity, which is increased in scleroderma patients, is a diagnostic marker for the determination of sclerotic activity in systemic sclerosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2013]

XYLT2 Gene-Disease associations (from GenCC):

• spondylo-ocular syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30329913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022167.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLT2	NM_022167.4	MANE Select	c.8C>T	p.Ala3Val	missense	Exon 1 of 11	NP_071450.2	Q9H1B5-1
	XYLT2	NR_110010.2		n.23C>T		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLT2	ENST00000017003.7	TSL:1 MANE Select	c.8C>T	p.Ala3Val	missense	Exon 1 of 11	ENSP00000017003.2	Q9H1B5-1
	XYLT2	ENST00000376550.7	TSL:1	n.8C>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000365733.3	A0A0C4DFW8
	XYLT2	ENST00000854775.1		c.8C>T	p.Ala3Val	missense	Exon 1 of 11	ENSP00000524834.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 147814 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 19 AN: 1109502 Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 12 AN XY: 545702

African (AFR) AF: 0.00 AC: 0 AN: 21440

American (AMR) AF: 0.0000539 AC: 1 AN: 18562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15578

East Asian (EAS) AF: 0.00 AC: 0 AN: 15936

South Asian (SAS) AF: 0.00 AC: 0 AN: 58960

European-Finnish (FIN) AF: 0.0000762 AC: 2 AN: 26232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2848

European-Non Finnish (NFE) AF: 0.0000165 AC: 15 AN: 909974

Other (OTH) AF: 0.0000250 AC: 1 AN: 39972

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 147814 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71964

African (AFR) AF: 0.00 AC: 0 AN: 41038

American (AMR) AF: 0.00 AC: 0 AN: 14876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3402

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66314

Other (OTH) AF: 0.00 AC: 0 AN: 2036

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T
Eigen	Benign	0.048
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.5
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.16
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.030	D
Polyphen		0.95	P
Vest4		0.49
MutPred		0.27		Gain of sheet (P = 0.0266)
MVP		0.24
MPC		0.66
ClinPred		0.97	D
GERP RS		3.2
PromoterAI		-0.26	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.45
gMVP		0.64
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1186744711; hg19: chr17-48423509;