Genetic Variant NM_022166.4:c.2827C>A (chr16-17108748-G-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_022166.4(XYLT1):c.2827C>A(p.Pro943Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

XYLT1
NM_022166.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.75

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XYLT1	NM_022166.4 link	c.2827C>A	p.Pro943Thr	missense_variant	Exon 12 of 12	ENST00000261381.7	NP_071449.1	Q86Y38
XYLT1	XM_047434458.1 link	c.2788C>A	p.Pro930Thr	missense_variant	Exon 11 of 11		XP_047290414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7 link	c.2827C>A	p.Pro943Thr	missense_variant	Exon 12 of 12	1	NM_022166.4	ENSP00000261381.6		Q86Y38

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453710

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.068

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.8

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-7.8

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.90

MutPred

0.50

Gain of phosphorylation at P943 (P = 0.0407);

MVP

0.42

MPC

0.88

ClinPred

1.0

GERP RS

4.7

Varity_R

0.85

gMVP

0.76

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over