NM_001037172.3:c.-54+2300A>T

Variant names:

• chr3-141234211-A-T
• rs2292402
• NM_001037172.3:c.-54+2300A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001037172.3(PXYLP1):​c.-54+2300A>T variant causes a 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 NM_001037172.3 intron
• Scores: Splicing: ADA: 0.00002403
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXYLP1	NM_001037172.3	MANE Select	c.-54+2300A>T		intron	N/A	NP_001032249.1
	PXYLP1	NM_152282.5		c.-227-5A>T		splice_region intron	N/A	NP_689495.1
	PXYLP1	NM_001282728.2		c.-266+2300A>T		intron	N/A	NP_001269657.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXYLP1	ENST00000286353.9	TSL:1 MANE Select	c.-54+2300A>T		intron	N/A	ENSP00000286353.4
	PXYLP1	ENST00000393010.6	TSL:1	c.-227-5A>T		splice_region intron	N/A	ENSP00000376733.2
	PXYLP1	ENST00000502783.5	TSL:2	c.-266+2300A>T		intron	N/A	ENSP00000422558.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.411 AC: 16948 AN: 41212

American (AMR) AF: 0.206 AC: 3140 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3466

East Asian (EAS) AF: 0.237 AC: 1221 AN: 5156

South Asian (SAS) AF: 0.0995 AC: 478 AN: 4804

European-Finnish (FIN) AF: 0.123 AC: 1287 AN: 10422

Middle Eastern (MID) AF: 0.224 AC: 65 AN: 290

European-Non Finnish (NFE) AF: 0.145 AC: 9865 AN: 67906

Other (OTH) AF: 0.210 AC: 442 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	15
DANN	Benign	0.36
PhyloP100		-0.0030
Mutation Taster		=33/67	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2292402; hg19: chr3-140953053;