Variant 6-3727577-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_183373.4(PXDC1):c.552G>C(p.Gln184His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,608,920 control chromosomes in the GnomAD database, including 351,580 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.66 ( 33190 hom., cov: 33)

Exomes 𝑓: 0.66 ( 318390 hom. )

Consequence

PXDC1
NM_183373.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.975

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.343562E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDC1	NM_183373.4 linkuse as main transcript	c.552G>C	p.Gln184His	missense_variant	4/5	ENST00000380283.5	NP_899229.2	Q5TGL8
PXDC1	XM_011514393.4 linkuse as main transcript	c.369G>C	p.Gln123His	missense_variant	5/6		XP_011512695.1
PXDC1	XM_047418376.1 linkuse as main transcript	c.369G>C	p.Gln123His	missense_variant	4/5		XP_047274332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PXDC1	ENST00000380283.5 linkuse as main transcript	c.552G>C	p.Gln184His	missense_variant	4/5	1	NM_183373.4	ENSP00000369636.5	Q5TGL8
PXDC1	ENST00000380277.6 linkuse as main transcript	c.393G>C	p.Gln131His	missense_variant	4/5	3		ENSP00000369630.2	H0Y3G1
PXDC1	ENST00000477592.2 linkuse as main transcript	n.548G>C		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes

AF:

0.659

AC:

100245

AN:

152004

Hom.:

33153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.666

Gnomad AMI

AF:

0.793

Gnomad AMR

AF:

0.606

Gnomad ASJ

AF:

0.694

Gnomad EAS

AF:

0.590

Gnomad SAS

AF:

0.673

Gnomad FIN

AF:

0.709

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.662

Gnomad OTH

AF:

0.634

GnomAD3 exomes

AF:

0.659

AC:

165564

AN:

251230

Hom.:

54727

AF XY:

0.662

AC XY:

89927

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.662

Gnomad AMR exome

AF:

0.617

Gnomad ASJ exome

AF:

0.705

Gnomad EAS exome

AF:

0.607

Gnomad SAS exome

AF:

0.679

Gnomad FIN exome

AF:

0.695

Gnomad NFE exome

AF:

0.663

Gnomad OTH exome

AF:

0.663

GnomAD4 exome

AF:

0.660

AC:

962092

AN:

1456798

Hom.:

318390

Cov.:

AF XY:

0.661

AC XY:

479486

AN XY:

725098

show subpopulations

Gnomad4 AFR exome

AF:

0.672

Gnomad4 AMR exome

AF:

0.617

Gnomad4 ASJ exome

AF:

0.701

Gnomad4 EAS exome

AF:

0.594

Gnomad4 SAS exome

AF:

0.678

Gnomad4 FIN exome

AF:

0.698

Gnomad4 NFE exome

AF:

0.660

Gnomad4 OTH exome

AF:

0.664

GnomAD4 genome

AF:

0.660

AC:

100326

AN:

152122

Hom.:

33190

Cov.:

AF XY:

0.659

AC XY:

48984

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.667

Gnomad4 AMR

AF:

0.605

Gnomad4 ASJ

AF:

0.694

Gnomad4 EAS

AF:

0.590

Gnomad4 SAS

AF:

0.674

Gnomad4 FIN

AF:

0.709

Gnomad4 NFE

AF:

0.662

Gnomad4 OTH

AF:

0.629

Alfa

AF:

0.669

Hom.:

11069

Bravo

AF:

0.654

TwinsUK

AF:

0.657

AC:

2437

ALSPAC

AF:

0.662

AC:

2551

ESP6500AA

AF:

0.655

AC:

2884

ESP6500EA

AF:

0.661

AC:

5681

ExAC

AF:

0.660

AC:

80115

Asia WGS

AF:

0.629

AC:

2189

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0074

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0000023

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.69

PrimateAI

Benign

0.32

PROVEAN

Benign

2.3

REVEL

Benign

0.10

Sift

Benign

0.29

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.034

MutPred

0.079

Gain of disorder (P = 0.1614);

MPC

0.38

ClinPred

0.010

GERP RS

4.5

Varity_R

0.045

gMVP

0.22

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over