3-141292489-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037172.3(PXYLP1):c.727G>A(p.Gly243Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PXYLP1 NM_001037172.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

Genes affected

PXYLP1 (HGNC:26303): (2-phosphoxylose phosphatase 1) Enables phosphatase activity. Involved in chondroitin sulfate proteoglycan biosynthetic process; glycosaminoglycan biosynthetic process; and positive regulation of heparan sulfate proteoglycan biosynthetic process. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21528417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXYLP1	NM_001037172.3	c.727G>A	p.Gly243Arg	missense_variant	6/6	ENST00000286353.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXYLP1	ENST00000286353.9	c.727G>A	p.Gly243Arg	missense_variant	6/6	1	NM_001037172.3	P1
	ENST00000507698.1	n.167-24881C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.727G>A (p.G243R) alteration is located in exon 8 (coding exon 5) of the PXYLP1 gene. This alteration results from a G to A substitution at nucleotide position 727, causing the glycine (G) at amino acid position 243 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.00097	T
BayesDel_noAF	Benign	-0.24
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.033	T;T;T;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.048
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.030	D;T;D;T;D
Sift4G	Uncertain	0.029	D;D;D;D;D
Polyphen		0.077	B;.;B;B;.
Vest4		0.39
MutPred		0.68		Loss of glycosylation at S242 (P = 0.1317);.;Loss of glycosylation at S242 (P = 0.1317);.;.;
MVP		0.48
MPC		0.30
ClinPred		0.49	T
GERP RS		5.5
Varity_R		0.14
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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.

Other links and lift over

hg19: chr3-141011331;