Variant 3-141278425-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001037172.3(PXYLP1):c.163C>G(p.Pro55Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXYLP1	NM_001037172.3 linkuse as main transcript	c.163C>G	p.Pro55Ala	missense_variant	3/6	ENST00000286353.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXYLP1	ENST00000286353.9 linkuse as main transcript	c.163C>G	p.Pro55Ala	missense_variant	3/6	1	NM_001037172.3	P1	Q8TE99-1
	ENST00000507698.1 linkuse as main transcript	n.167-10817G>C		intron_variant, non_coding_transcript_variant		3
	ENST00000663611.1 linkuse as main transcript	n.172+5710G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251478

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jun 07, 2024

The c.163C>G (p.P55A) alteration is located in exon 5 (coding exon 2) of the PXYLP1 gene. This alteration results from a C to G substitution at nucleotide position 163, causing the proline (P) at amino acid position 55 to be replaced by an alanine (A). 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

Benign

0.080

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

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

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

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

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.56

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

MetaSVM

Uncertain

-0.24

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-6.3

D;N;N;N;D;D;N;N

REVEL

Uncertain

0.42

Sift

Uncertain

0.012

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

Sift4G

Uncertain

0.029

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

Polyphen

0.96, 0.98

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

Vest4

0.66, 0.64, 0.67, 0.68

MutPred

0.55

Loss of disorder (P = 0.0524);Loss of disorder (P = 0.0524);.;Loss of disorder (P = 0.0524);Loss of disorder (P = 0.0524);.;.;.;

MVP

0.54

MPC

0.27

ClinPred

0.79

GERP RS

5.8

Varity_R

0.055

gMVP

0.55

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

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