Variant chr3-141279459-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001037172.3(PXYLP1):c.320C>T(p.Pro107Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PXYLP1
NM_001037172.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXYLP1	NM_001037172.3 linkuse as main transcript	c.320C>T	p.Pro107Leu	missense_variant	4/6	ENST00000286353.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXYLP1	ENST00000286353.9 linkuse as main transcript	c.320C>T	p.Pro107Leu	missense_variant	4/6	1	NM_001037172.3	P1	Q8TE99-1
	ENST00000507698.1 linkuse as main transcript	n.167-11851G>A		intron_variant, non_coding_transcript_variant		3
	ENST00000663611.1 linkuse as main transcript	n.172+4676G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

The c.320C>T (p.P107L) alteration is located in exon 6 (coding exon 3) of the PXYLP1 gene. This alteration results from a C to T substitution at nucleotide position 320, causing the proline (P) at amino acid position 107 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.0069

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T;T;T;.;T;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.99

D;.;D;D;D;D;D

M_CAP

Benign

0.078

MetaRNN

Pathogenic

0.76

D;D;D;D;D;D;D

MetaSVM

Benign

-0.68

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-9.0

D;D;D;D;D;D;D

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;T;T;T;D;T;T

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

1.0

.;D;.;D;.;D;.

Vest4

0.94, 0.94, 0.94, 0.93, 0.94

MutPred

0.78

Loss of methylation at K108 (P = 0.0459);Loss of methylation at K108 (P = 0.0459);.;Loss of methylation at K108 (P = 0.0459);.;.;.;

MVP

0.49

MPC

0.88

ClinPred

1.0

GERP RS

5.0

Varity_R

0.30

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over