16-17470454-C-T

Variant names:

• chr16-17470454-C-T
• rs61758388
• NM_022166.4:c.343G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022166.4(XYLT1):​c.343G>A​(p.Ala115Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000927 in 1,078,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A115S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: XYLT1 NM_022166.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397
• Publications: 0 publications found

Genes affected

XYLT1 (HGNC:15516): (xylosyltransferase 1) This locus encodes a xylosyltransferase enzyme. The encoded protein catalyzes transfer of UDP-xylose to serine residues of an acceptor protein substrate. This transfer reaction is necessary for biosynthesis of glycosaminoglycan chains. Mutations in this gene have been associated with increased severity of pseudoxanthoma elasticum.[provided by RefSeq, Nov 2009]

XYLT1 Gene-Disease associations (from GenCC):

• Desbuquois dysplasia 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Desbuquois dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• XYLT1-congenital disorder of glycosylation

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC107987234 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050266534).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022166.4. 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
	XYLT1	NM_022166.4	MANE Select	c.343G>A	p.Ala115Thr	missense	Exon 1 of 12	NP_071449.1	Q86Y38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLT1	ENST00000261381.7	TSL:1 MANE Select	c.343G>A	p.Ala115Thr	missense	Exon 1 of 12	ENSP00000261381.6	Q86Y38
	XYLT1	ENST00000933757.1		c.343G>A	p.Ala115Thr	missense	Exon 1 of 12	ENSP00000603816.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.27e-7 AC: 1 AN: 1078702 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 510140

African (AFR) AF: 0.00 AC: 0 AN: 22736

American (AMR) AF: 0.00 AC: 0 AN: 8306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14182

East Asian (EAS) AF: 0.00 AC: 0 AN: 26402

South Asian (SAS) AF: 0.00 AC: 0 AN: 20234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3232

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 919112

Other (OTH) AF: 0.00 AC: 0 AN: 43426

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.28	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.40
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.026
Sift	Benign	0.15	T
Sift4G	Benign	0.47	T
Polyphen		0.0010	B
Vest4		0.014
MutPred		0.15		Gain of phosphorylation at A115 (P = 0.0104)
MVP		0.043
MPC		0.21
ClinPred		0.059	T
GERP RS		1.8
Varity_R		0.070
gMVP		0.11

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

Other links and lift over

dbSNP: rs61758388; hg19: chr16-17564311;