NM_022166.4:c.2784G>A

Variant names:

• chr16-17108791-C-T
• rs150334363
• NM_022166.4:c.2784G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2 BP4_Strong BP6_Moderate BP7 BS1

The NM_022166.4(XYLT1):​c.2784G>A​(p.Pro928Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,611,216 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000039 (1 hom.)
• Consequence: XYLT1 NM_022166.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -9.70
• 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: G2P, Labcorp Genetics (formerly Invitae)
• Desbuquois dysplasia

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000261448 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-17108791-C-T is Benign according to our data. Variant chr16-17108791-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1458293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-9.7 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000722 (11/152314) while in subpopulation AFR AF = 0.000192 (8/41566). AF 95% confidence interval is 0.0000954. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.2784G>A	p.Pro928Pro	synonymous	Exon 12 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.2784G>A	p.Pro928Pro	synonymous	Exon 12 of 12	ENSP00000261381.6	Q86Y38
	XYLT1	ENST00000933757.1		c.2781G>A	p.Pro927Pro	synonymous	Exon 12 of 12	ENSP00000603816.1
	ENSG00000261448	ENST00000567344.2	TSL:3	n.349-25675C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000725 AC: 18 AN: 248406 AF XY: 0.0000966

Gnomad AFR exome AF: 0.000248

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.000202

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000391 AC: 57 AN: 1458902 Hom.: 1 Cov.: 30 AF XY: 0.0000523 AC XY: 38 AN XY: 725918

African (AFR) AF: 0.000149 AC: 5 AN: 33466

American (AMR) AF: 0.0000448 AC: 2 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86180

European-Finnish (FIN) AF: 0.000254 AC: 13 AN: 51102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5518

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111792

Other (OTH) AF: 0.0000994 AC: 6 AN: 60346

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74474

African (AFR) AF: 0.000192 AC: 8 AN: 41566

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000281 Hom.: 0

Bravo AF: 0.0000756

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Desbuquois dysplasia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.026
DANN	Benign	0.53
PhyloP100		-9.7

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: rs150334363; hg19: chr16-17202648;