rs1444261356

Variant names:

• chr16-17108710-A-G
• rs1444261356
• NM_022166.4:c.2865T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_022166.4(XYLT1):​c.2865T>C​(p.Asp955Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,428,602 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: XYLT1 NM_022166.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.170
• 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

ENSG00000261448 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 16-17108710-A-G is Benign according to our data. Variant chr16-17108710-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1107654.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.17 with no splicing effect.

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.2865T>C	p.Asp955Asp	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.2865T>C	p.Asp955Asp	synonymous	Exon 12 of 12	ENSP00000261381.6	Q86Y38
	XYLT1	ENST00000933757.1		c.2862T>C	p.Asp954Asp	synonymous	Exon 12 of 12	ENSP00000603816.1
	ENSG00000261448	ENST00000567344.2	TSL:3	n.349-25756A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000850 AC: 2 AN: 235250 AF XY: 0.0000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000329 AC: 47 AN: 1428602 Hom.: 0 Cov.: 30 AF XY: 0.0000311 AC XY: 22 AN XY: 706896

African (AFR) AF: 0.00 AC: 0 AN: 33128

American (AMR) AF: 0.00 AC: 0 AN: 43958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25326

East Asian (EAS) AF: 0.00 AC: 0 AN: 39164

South Asian (SAS) AF: 0.00 AC: 0 AN: 84028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4732

European-Non Finnish (NFE) AF: 0.0000401 AC: 44 AN: 1096462

Other (OTH) AF: 0.0000507 AC: 3 AN: 59190

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

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	-0.63
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1444261356; hg19: chr16-17202567;