chr3-141292788-C-T

Variant names:

• chr3-141292788-C-T
• rs3210458
• NM_001037172.3:c.1026C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_152282.5(PXYLP1):​c.1026C>T​(p.Phe342Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 1,613,050 control chromosomes in the GnomAD database, including 6,796 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.088 (637 hom., cov: 32)
  • Exomes 𝑓: 0.090 (6159 hom.)
• Consequence: PXYLP1 NM_152282.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 13 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-0.526 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152282.5. 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.1026C>T	p.Phe342Phe	synonymous	Exon 6 of 6	NP_001032249.1
	PXYLP1	NM_152282.5		c.1026C>T	p.Phe342Phe	synonymous	Exon 8 of 8	NP_689495.1
	PXYLP1	NM_001282728.2		c.912C>T	p.Phe304Phe	synonymous	Exon 7 of 7	NP_001269657.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXYLP1	ENST00000286353.9	TSL:1 MANE Select	c.1026C>T	p.Phe342Phe	synonymous	Exon 6 of 6	ENSP00000286353.4
	PXYLP1	ENST00000393010.6	TSL:1	c.1026C>T	p.Phe342Phe	synonymous	Exon 8 of 8	ENSP00000376733.2
	PXYLP1	ENST00000508812.1	TSL:1	c.999C>T	p.Phe333Phe	synonymous	Exon 5 of 5	ENSP00000422901.1

Frequencies

GnomAD3 genomes AF: 0.0885 AC: 13460 AN: 152100 Hom.: 638 Cov.: 32

Gnomad AFR AF: 0.0887

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0898

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.0889

GnomAD2 exomes AF: 0.0843 AC: 21102 AN: 250188 AF XY: 0.0866

Gnomad AFR exome AF: 0.0851

Gnomad AMR exome AF: 0.0664

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.101

Gnomad FIN exome AF: 0.0506

Gnomad NFE exome AF: 0.0880

Gnomad OTH exome AF: 0.0901

GnomAD4 exome AF: 0.0903 AC: 131951 AN: 1460832 Hom.: 6159 Cov.: 31 AF XY: 0.0906 AC XY: 65809 AN XY: 726650

African (AFR) AF: 0.0922 AC: 3084 AN: 33446

American (AMR) AF: 0.0674 AC: 3006 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3357 AN: 26026

East Asian (EAS) AF: 0.123 AC: 4872 AN: 39698

South Asian (SAS) AF: 0.0908 AC: 7818 AN: 86074

European-Finnish (FIN) AF: 0.0528 AC: 2816 AN: 53382

Middle Eastern (MID) AF: 0.148 AC: 850 AN: 5760

European-Non Finnish (NFE) AF: 0.0904 AC: 100524 AN: 1111496

Other (OTH) AF: 0.0932 AC: 5624 AN: 60350

GnomAD4 genome AF: 0.0884 AC: 13452 AN: 152218 Hom.: 637 Cov.: 32 AF XY: 0.0865 AC XY: 6439 AN XY: 74424

African (AFR) AF: 0.0885 AC: 3678 AN: 41542

American (AMR) AF: 0.0953 AC: 1458 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3472

East Asian (EAS) AF: 0.113 AC: 581 AN: 5158

South Asian (SAS) AF: 0.0892 AC: 430 AN: 4820

European-Finnish (FIN) AF: 0.0489 AC: 519 AN: 10610

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0881 AC: 5989 AN: 68004

Other (OTH) AF: 0.0875 AC: 185 AN: 2114

Alfa AF: 0.0877 Hom.: 1195

Bravo AF: 0.0908

EpiCase AF: 0.0975

EpiControl AF: 0.0945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.5
DANN	Benign	0.86
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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: rs3210458; hg19: chr3-141011630; COSMIC: COSV53892670; COSMIC: COSV53892670;