Genetic Variant PDZD4:p.Ala476Ala (chrX-153804253-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001303512.2(PDZD4):c.1428C>T(p.Ala476Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000796 in 1,207,738 control chromosomes in the GnomAD database, including 2 homozygotes. There are 298 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00057 ( 1 hom., 18 hem., cov: 25)

Exomes 𝑓: 0.00082 ( 1 hom. 280 hem. )

Consequence

PDZD4
NM_001303512.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.83

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-153804253-G-A is Benign according to our data. Variant chrX-153804253-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2661736.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 18 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	UniProt
PDZD4	NM_001303512.2	MANE Select	c.1428C>T	p.Ala476Ala	synonymous	Exon 8 of 8	NP_001290441.1	Q17RL8
PDZD4	NM_032512.5		c.1410C>T	p.Ala470Ala	synonymous	Exon 8 of 8	NP_115901.2
PDZD4	NM_001303515.2		c.1185C>T	p.Ala395Ala	synonymous	Exon 8 of 8	NP_001290444.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDZD4	ENST00000393758.7	TSL:1 MANE Select	c.1428C>T	p.Ala476Ala	synonymous	Exon 8 of 8	ENSP00000377355.3	Q17RL8
PDZD4	ENST00000164640.8	TSL:1	c.1410C>T	p.Ala470Ala	synonymous	Exon 8 of 8	ENSP00000164640.4	Q76G19-1
PDZD4	ENST00000544474.5	TSL:1	c.1083C>T	p.Ala361Ala	synonymous	Exon 6 of 6	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes

AF:

0.000574

AC:

AN:

113253

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000320

Gnomad AMI

AF:

0.0206

Gnomad AMR

AF:

0.000184

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00111

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.000648

GnomAD2 exomes

AF:

0.000546

AC:

AN:

175847

AF XY:

0.000439

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000960

Gnomad NFE exome

AF:

0.000947

Gnomad OTH exome

AF:

0.000693

GnomAD4 exome

AF:

0.000819

AC:

896

AN:

1094431

Hom.:

Cov.:

AF XY:

0.000775

AC XY:

280

AN XY:

361119

show subpopulations

African (AFR)

AF:

0.0000759

AC:

AN:

26358

American (AMR)

AF:

0.000171

AC:

AN:

35148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19358

East Asian (EAS)

AF:

0.00

AC:

AN:

30149

South Asian (SAS)

AF:

0.00

AC:

AN:

53961

European-Finnish (FIN)

AF:

0.00124

AC:

AN:

38673

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3630

European-Non Finnish (NFE)

AF:

0.000963

AC:

810

AN:

841262

Other (OTH)

AF:

0.000654

AC:

AN:

45892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

130

174

217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.000574

AC:

AN:

113307

Hom.:

Cov.:

AF XY:

0.000508

AC XY:

AN XY:

35453

show subpopulations

African (AFR)

AF:

0.0000319

AC:

AN:

31300

American (AMR)

AF:

0.000184

AC:

AN:

10870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2659

East Asian (EAS)

AF:

0.00

AC:

AN:

3578

South Asian (SAS)

AF:

0.00

AC:

AN:

2824

European-Finnish (FIN)

AF:

0.00111

AC:

AN:

6322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000751

AC:

AN:

53296

Other (OTH)

AF:

0.000640

AC:

AN:

1562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.000261

Hom.:

Bravo

AF:

0.000706

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

1.8

Mutation Taster

=100/0

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