Variant chr6-3738143-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_183373.4(PXDC1):c.262G>A(p.Val88Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

PXDC1
NM_183373.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.695

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040599525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDC1	NM_183373.4 linkuse as main transcript	c.262G>A	p.Val88Ile	missense_variant	2/5	ENST00000380283.5	NP_899229.2	Q5TGL8
PXDC1	XM_011514393.4 linkuse as main transcript	c.79G>A	p.Val27Ile	missense_variant	3/6		XP_011512695.1
PXDC1	XM_047418376.1 linkuse as main transcript	c.79G>A	p.Val27Ile	missense_variant	2/5		XP_047274332.1
PXDC1	XR_007059222.1 linkuse as main transcript	n.444G>A		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PXDC1	ENST00000380283.5 linkuse as main transcript	c.262G>A	p.Val88Ile	missense_variant	2/5	1	NM_183373.4	ENSP00000369636.5	Q5TGL8
PXDC1	ENST00000380277.6 linkuse as main transcript	c.103G>A	p.Val35Ile	missense_variant	2/5	3		ENSP00000369630.2	H0Y3G1
PXDC1	ENST00000477592.2 linkuse as main transcript	n.263G>A		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000437

AC:

AN:

251438

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1461146

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000382

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Apr 25, 2022

The c.262G>A (p.V88I) alteration is located in exon 2 (coding exon 2) of the PXDC1 gene. This alteration results from a G to A substitution at nucleotide position 262, causing the valine (V) at amino acid position 88 to be replaced by an isoleucine (I). 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

0.087

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.015

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.75

M_CAP

Benign

0.0058

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.34

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.060

REVEL

Benign

0.017

Sift

Benign

0.55

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.15

MVP

0.082

MPC

0.33

ClinPred

0.043

GERP RS

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.5

Varity_R

0.025

gMVP

0.15

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