Genetic Variant PSD3:c.21+12834C>T (chr8-19000729-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015310.4(PSD3):c.21+12834C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,720 control chromosomes in the GnomAD database, including 8,459 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 0.32 ( 8458 hom., cov: 32)

Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

PSD3
NM_015310.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00800

Publications

4 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:

ENSG00000253335 (HGNC:):

ENSG00000253335 links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015310.4. 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.21+12834C>T	intron	N/A	NP_056125.3
PSD3	NM_001412866.1		c.325-64587C>T	intron	N/A	NP_001399795.1
PSD3	NM_001412865.1		c.325-64587C>T	intron	N/A	NP_001399794.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PSD3	ENST00000327040.13	TSL:1 MANE Select	c.21+12834C>T	intron	N/A	ENSP00000324127.8
ENSG00000253335	ENST00000522670.1	TSL:4	n.322G>A	non_coding_transcript_exon	Exon 3 of 3
PSD3	ENST00000521475.1	TSL:2	c.325-64587C>T	intron	N/A	ENSP00000428405.1

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48625

AN:

151596

Hom.:

8460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.313

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

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:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.321

AC:

48640

AN:

151716

Hom.:

8458

Cov.:

AF XY:

0.319

AC XY:

23644

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.235

AC:

9711

AN:

41354

American (AMR)

AF:

0.269

AC:

4102

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

835

AN:

3462

East Asian (EAS)

AF:

0.404

AC:

2086

AN:

5162

South Asian (SAS)

AF:

0.318

AC:

1512

AN:

4758

European-Finnish (FIN)

AF:

0.412

AC:

4348

AN:

10564

Middle Eastern (MID)

AF:

0.264

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.367

AC:

24907

AN:

67846

Other (OTH)

AF:

0.312

AC:

657

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1666

3332

4998

6664

8330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.333

Hom.:

15255

Bravo

AF:

0.309

Asia WGS

AF:

0.355

AC:

1233

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

(source)

DANN

Benign

0.76

PhyloP100

0.0080

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