Genetic Variant NM_001303512.2:c.1514A>G (chrX-153804167-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001303512.2(PDZD4):c.1514A>G(p.Asn505Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00043 in 1,172,612 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 160 hemizygotes in GnomAD. 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 0.00014 ( 0 hom., 4 hem., cov: 25)

Exomes 𝑓: 0.00046 ( 0 hom. 156 hem. )

Consequence

PDZD4
NM_001303512.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

Publications

0 publications found

Variant links:

Genes affected

PDZD4 (HGNC:21167): (PDZ domain containing 4) Predicted to be located in cell cortex. [provided by Alliance of Genome Resources, Apr 2022]

PDZD4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017238766).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303512.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDZD4	NM_001303512.2	MANE Select	c.1514A>G	p.Asn505Ser	missense	Exon 8 of 8	NP_001290441.1
PDZD4	NM_032512.5		c.1496A>G	p.Asn499Ser	missense	Exon 8 of 8	NP_115901.2
PDZD4	NM_001303515.2		c.1271A>G	p.Asn424Ser	missense	Exon 8 of 8	NP_001290444.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDZD4	ENST00000393758.7	TSL:1 MANE Select	c.1514A>G	p.Asn505Ser	missense	Exon 8 of 8	ENSP00000377355.3
PDZD4	ENST00000164640.8	TSL:1	c.1496A>G	p.Asn499Ser	missense	Exon 8 of 8	ENSP00000164640.4
PDZD4	ENST00000544474.5	TSL:1	c.1169A>G	p.Asn390Ser	missense	Exon 6 of 6	ENSP00000442033.1

Frequencies

GnomAD3 genomes

AF:

0.000142

AC:

AN:

112291

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000323

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000245

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000116

AC:

AN:

120375

AF XY:

0.0000917

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 FIN exome

AF:

0.000339

Gnomad NFE exome

AF:

0.000224

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000460

AC:

488

AN:

1060270

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

156

AN XY:

340770

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25658

American (AMR)

AF:

0.0000329

AC:

AN:

30383

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18519

East Asian (EAS)

AF:

0.00

AC:

AN:

28562

South Asian (SAS)

AF:

0.00

AC:

AN:

50762

European-Finnish (FIN)

AF:

0.000178

AC:

AN:

33714

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3604

European-Non Finnish (NFE)

AF:

0.000573

AC:

472

AN:

824417

Other (OTH)

AF:

0.000202

AC:

AN:

44651

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000142

AC:

AN:

112342

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34620

show subpopulations

African (AFR)

AF:

0.0000322

AC:

AN:

31021

American (AMR)

AF:

0.00

AC:

AN:

10787

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3518

South Asian (SAS)

AF:

0.00

AC:

AN:

2755

European-Finnish (FIN)

AF:

0.000323

AC:

AN:

6196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000245

AC:

AN:

52999

Other (OTH)

AF:

0.00

AC:

AN:

1534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000459

AC:

ExAC

AF:

0.000120

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.91

CADD

Benign

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.068

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.72

M_CAP

Benign

0.030

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.60

PhyloP100

1.8

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.040

REVEL

Benign

0.11

Sift

Benign

0.96

Sift4G

Benign

0.93

Polyphen

0.26

Vest4

0.14

MVP

0.40

MPC

0.74

ClinPred

0.057

GERP RS

5.3

Varity_R

0.056

gMVP

0.15

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over