Variant 6-3737108-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_183373.4(PXDC1):c.437C>T(p.Pro146Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

PXDC1
NM_183373.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.56

Variant links:

Genes affected

PXDC1 (HGNC:21361): (PX domain containing 1) Predicted to enable phosphatidylinositol binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PXDC1 links:

PXDC1 (HGNC:):

PXDC1 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	Protein	UniProt
PXDC1	NM_183373.4 linkuse as main transcript	c.437C>T	p.Pro146Leu	missense_variant	3/5	ENST00000380283.5	NP_899229.2	Q5TGL8
PXDC1	XM_011514393.4 linkuse as main transcript	c.254C>T	p.Pro85Leu	missense_variant	4/6		XP_011512695.1
PXDC1	XM_047418376.1 linkuse as main transcript	c.254C>T	p.Pro85Leu	missense_variant	3/5		XP_047274332.1
PXDC1	XR_007059222.1 linkuse as main transcript	n.*3C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PXDC1	ENST00000380283.5 linkuse as main transcript	c.437C>T	p.Pro146Leu	missense_variant	3/5	1	NM_183373.4	ENSP00000369636.5	Q5TGL8
PXDC1	ENST00000380277.6 linkuse as main transcript	c.278C>T	p.Pro93Leu	missense_variant	3/5	3		ENSP00000369630.2	H0Y3G1
PXDC1	ENST00000477592.2 linkuse as main transcript	n.433C>T		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251436

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460038

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726516

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:

0.00000811

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Oct 04, 2022

The c.437C>T (p.P146L) alteration is located in exon 3 (coding exon 3) of the PXDC1 gene. This alteration results from a C to T substitution at nucleotide position 437, causing the proline (P) at amino acid position 146 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

Benign

0.18

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.1

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-7.2

REVEL

Uncertain

0.40

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0070

Polyphen

0.80

Vest4

0.72

MutPred

0.49

Gain of sheet (P = 0.0028);

MVP

0.27

MPC

0.46

ClinPred

0.98

GERP RS

4.0

Varity_R

0.50

gMVP

0.71

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