dbSNP rs3736273: PSD3:c.1634+2655T>C (chr8-18865019-A-G) – 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.1937+2655T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 150,734 control chromosomes in the GnomAD database, including 10,928 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 0.36 ( 10928 hom., cov: 26)

Exomes 𝑓: 0.22 ( 0 hom. )

Consequence

PSD3
NM_001412866.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.525

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:

ENSG00000278886 (HGNC:):

ENSG00000278886 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 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.1634+2655T>C	intron	N/A	NP_056125.3
PSD3	NM_001412866.1		c.1937+2655T>C	intron	N/A	NP_001399795.1
PSD3	NM_001412865.1		c.1937+2655T>C	intron	N/A	NP_001399794.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PSD3	ENST00000327040.13	TSL:1 MANE Select	c.1634+2655T>C	intron	N/A	ENSP00000324127.8
PSD3	ENST00000523619.5	TSL:1	c.1439+2655T>C	intron	N/A	ENSP00000430640.1
ENSG00000278886	ENST00000623639.1	TSL:6	n.229T>C	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

54788

AN:

150598

Hom.:

10927

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.542

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.691

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.368

GnomAD4 exome

AF:

0.222

AC:

AN:

Hom.:

Cov.:

AF XY:

0.100

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:

0.214

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.364

AC:

54794

AN:

150716

Hom.:

10928

Cov.:

AF XY:

0.358

AC XY:

26316

AN XY:

73522

show subpopulations

African (AFR)

AF:

0.227

AC:

9358

AN:

41164

American (AMR)

AF:

0.314

AC:

4734

AN:

15092

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1301

AN:

3464

East Asian (EAS)

AF:

0.691

AC:

3512

AN:

5084

South Asian (SAS)

AF:

0.418

AC:

1960

AN:

4694

European-Finnish (FIN)

AF:

0.290

AC:

2993

AN:

10316

Middle Eastern (MID)

AF:

0.370

AC:

108

AN:

292

European-Non Finnish (NFE)

AF:

0.437

AC:

29570

AN:

67618

Other (OTH)

AF:

0.368

AC:

767

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1473

2945

4418

5890

7363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.318

Hom.:

1545

Bravo

AF:

0.361

Asia WGS

AF:

0.510

AC:

1768

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.0

(source)

DANN

Benign

0.39

PhyloP100

0.53

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