Genetic Variant PSD3:c.*5212G>A (chr8-18530531-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001412866.1(PSD3):c.*5212G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,518 control chromosomes in the GnomAD database, including 45,962 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.76 ( 45804 hom., cov: 32)

Exomes 𝑓: 0.87 ( 158 hom. )

Consequence

PSD3
NM_001412866.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0800

Publications

11 publications found

Variant links:

Genes affected

PSD3 (HGNC:19093): (pleckstrin and Sec7 domain containing 3) Predicted to enable guanyl-nucleotide exchange factor activity and phospholipid binding activity. Predicted to be involved in regulation of ARF protein signal transduction and regulation of catalytic activity. Predicted to be located in membrane. Predicted to be active in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

PSD3 Gene-Disease associations (from GenCC):

antecubital pterygium syndrome
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

PSD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001412866.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PSD3	NM_015310.4	MANE Select	c.*5212G>A	3_prime_UTR	Exon 16 of 16	NP_056125.3
PSD3	NM_001412866.1		c.*5212G>A	3_prime_UTR	Exon 17 of 17	NP_001399795.1
PSD3	NM_001412865.1		c.*5212G>A	3_prime_UTR	Exon 16 of 16	NP_001399794.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PSD3	ENST00000327040.13	TSL:1 MANE Select	c.*5212G>A	3_prime_UTR	Exon 16 of 16	ENSP00000324127.8
PSD3	ENST00000523619.5	TSL:1	c.*5212G>A	downstream_gene	N/A	ENSP00000430640.1
PSD3	ENST00000286485.12	TSL:1	c.*5212G>A	downstream_gene	N/A	ENSP00000286485.8

Frequencies

GnomAD3 genomes

AF:

0.758

AC:

115164

AN:

151974

Hom.:

45793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.823

Gnomad AMR

AF:

0.854

Gnomad ASJ

AF:

0.863

Gnomad EAS

AF:

0.899

Gnomad SAS

AF:

0.683

Gnomad FIN

AF:

0.889

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.864

Gnomad OTH

AF:

0.796

GnomAD4 exome

AF:

0.869

AC:

370

AN:

426

Hom.:

158

Cov.:

AF XY:

0.867

AC XY:

222

AN XY:

256

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.869

AC:

365

AN:

420

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.757

AC:

115194

AN:

152092

Hom.:

45804

Cov.:

AF XY:

0.760

AC XY:

56557

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.490

AC:

20291

AN:

41398

American (AMR)

AF:

0.855

AC:

13064

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

2995

AN:

3472

East Asian (EAS)

AF:

0.899

AC:

4652

AN:

5174

South Asian (SAS)

AF:

0.683

AC:

3295

AN:

4822

European-Finnish (FIN)

AF:

0.889

AC:

9429

AN:

10612

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.864

AC:

58797

AN:

68014

Other (OTH)

AF:

0.796

AC:

1682

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1231

2463

3694

4926

6157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.835

Hom.:

96406

Bravo

AF:

0.748

Asia WGS

AF:

0.776

AC:

2700

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.2

(source)

DANN

Benign

0.85

PhyloP100

-0.080

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over