Genetic Variant PXYLP1:p.Phe342Phe (chr3-141292788-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001037172.3(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_001037172.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.526

Publications

13 publications found

Variant links:

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]

PXYLP1 links:

ENSG00000249417 (HGNC:):

ENSG00000249417 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXYLP1	NM_001037172.3 link	c.1026C>T	p.Phe342Phe	synonymous_variant	Exon 6 of 6	ENST00000286353.9	NP_001032249.1	Q8TE99-1Q9NT50

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXYLP1	ENST00000286353.9 link	c.1026C>T	p.Phe342Phe	synonymous_variant	Exon 6 of 6	1	NM_001037172.3	ENSP00000286353.4		Q8TE99-1

Frequencies

GnomAD3 genomes

AF:

0.0885

AC:

13460

AN:

152100

Hom.:

638

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0906

AC XY:

65809

AN XY:

726650

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

7980

15960

23941

31921

39901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0884

AC:

13452

AN:

152218

Hom.:

637

Cov.:

AF XY:

0.0865

AC XY:

6439

AN XY:

74424

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0881

AC:

5989

AN:

68004

Other (OTH)

AF:

0.0875

AC:

185

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

623

1246

1869

2492

3115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.5

(source)

DANN

Benign

0.86

PhyloP100

-0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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chr3-141292788-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over