3-141234211-A-T

Position:

• chr3-141234211-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000393010.6(PXYLP1):​c.-227-5A>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,528 control chromosomes in the GnomAD database, including 4,942 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 0.22 (4941 hom., cov: 31)
  • Exomes 𝑓: 0.25 (1 hom.)
• Consequence: PXYLP1 ENST00000393010.6 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002403
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXYLP1	NM_001037172.3	c.-54+2300A>T		intron_variant		ENST00000286353.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXYLP1	ENST00000286353.9	c.-54+2300A>T		intron_variant		1	NM_001037172.3	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34059 AN: 151402 Hom.: 4941 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.250 AC: 3 AN: 12 Hom.: 1 Cov.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.225 AC: 34089 AN: 151516 Hom.: 4941 Cov.: 31 AF XY: 0.223 AC XY: 16488 AN XY: 73980

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.0995

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.210

Alfa AF: 0.0786 Hom.: 108

Bravo AF: 0.238

Asia WGS AF: 0.201 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	15
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2292402; hg19: chr3-140953053;