rs753267121

Variant names:

• chr3-141292475-C-A
• rs753267121
• NM_001037172.3:c.713C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-141292475-C-A
• chr3-141292475-C-G
• chr3-141292475-C-T

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.713C>A​(p.Ala238Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A238V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PXYLP1 NM_001037172.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.01
• Publications: 2 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=0.2559448).

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.713C>A	p.Ala238Glu	missense	Exon 6 of 6	NP_001032249.1	Q8TE99-1
	PXYLP1	NM_152282.5		c.713C>A	p.Ala238Glu	missense	Exon 8 of 8	NP_689495.1	Q8TE99-1
	PXYLP1	NM_001282728.2		c.599C>A	p.Ala200Glu	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.713C>A	p.Ala238Glu	missense	Exon 6 of 6	ENSP00000286353.4	Q8TE99-1
	PXYLP1	ENST00000393010.6	TSL:1	c.713C>A	p.Ala238Glu	missense	Exon 8 of 8	ENSP00000376733.2	Q8TE99-1
	PXYLP1	ENST00000508812.1	TSL:1	c.686C>A	p.Ala229Glu	missense	Exon 5 of 5	ENSP00000422901.1	E9PDB7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.18
Sift	Benign	0.084	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.91	P
Vest4		0.21
MutPred		0.64		Gain of solvent accessibility (P = 0.0488)
MVP		0.21
MPC		0.77
ClinPred		0.84	D
GERP RS		4.6
Varity_R		0.14
gMVP		0.81
Mutation Taster		=46/54	disease causing

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: rs753267121; hg19: chr3-141011317;