NM_001037172.3:c.727G>A

Variant names:

• chr3-141292489-G-A
• NM_001037172.3:c.727G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 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
• Publications: 0 publications found

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]

ENSG00000249417 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037172.3. 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
	PXYLP1	NM_001037172.3	MANE Select	c.727G>A	p.Gly243Arg	missense	Exon 6 of 6	NP_001032249.1	Q8TE99-1
	PXYLP1	NM_152282.5		c.727G>A	p.Gly243Arg	missense	Exon 8 of 8	NP_689495.1	Q8TE99-1
	PXYLP1	NM_001282728.2		c.613G>A	p.Gly205Arg	missense	Exon 7 of 7	NP_001269657.1	B7Z4T2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXYLP1	ENST00000286353.9	TSL:1 MANE Select	c.727G>A	p.Gly243Arg	missense	Exon 6 of 6	ENSP00000286353.4	Q8TE99-1
	PXYLP1	ENST00000393010.6	TSL:1	c.727G>A	p.Gly243Arg	missense	Exon 8 of 8	ENSP00000376733.2	Q8TE99-1
	PXYLP1	ENST00000508812.1	TSL:1	c.700G>A	p.Gly234Arg	missense	Exon 5 of 5	ENSP00000422901.1	E9PDB7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.048
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.81	T
PhyloP100		2.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.30
Sift	Benign	0.030	D
Sift4G	Uncertain	0.029	D
Polyphen		0.077	B
Vest4		0.39
MutPred		0.68		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
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

hg19: chr3-141011331;