dbSNP rs762698574: PSD3:p.Met982Ile (chr8-18535941-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015310.4(PSD3):c.2946G>A(p.Met982Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PSD3
NM_015310.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.833

Publications

0 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: Unknown Classification: LIMITED Submitted by: ClinGen

PSD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013145119).

BP6

Variant 8-18535941-C-T is Benign according to our data. Variant chr8-18535941-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3784229.Status of the report is criteria_provided_single_submitter, 1 stars.

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	HGVSp	Effect	Exon Rank	Protein
PSD3	NM_015310.4	MANE Select	c.2946G>A	p.Met982Ile	missense	Exon 16 of 16	NP_056125.3
PSD3	NM_001412866.1		c.3330G>A	p.Met1110Ile	missense	Exon 17 of 17	NP_001399795.1
PSD3	NM_001412865.1		c.3249G>A	p.Met1083Ile	missense	Exon 16 of 16	NP_001399794.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSD3	ENST00000327040.13	TSL:1 MANE Select	c.2946G>A	p.Met982Ile	missense	Exon 16 of 16	ENSP00000324127.8	Q9NYI0-2
PSD3	ENST00000523619.5	TSL:1	c.2751G>A	p.Met917Ile	missense	Exon 15 of 15	ENSP00000430640.1	E5RJ29
PSD3	ENST00000286485.12	TSL:1	c.1344G>A	p.Met448Ile	missense	Exon 13 of 13	ENSP00000286485.8	Q9NYI0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251144

AF XY:

0.00000737

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:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111980

Other (OTH)

AF:

0.00

AC:

AN:

60396

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

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.093

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.010

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.015

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.76

M_CAP

Benign

0.0020

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

PhyloP100

-0.83

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.12

REVEL

Benign

0.036

Sift

Benign

1.0

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.048

MutPred

0.40

Gain of catalytic residue at L988 (P = 0.0329)

MVP

0.043

MPC

0.020

ClinPred

0.023

GERP RS

-12

Varity_R

0.070

gMVP

0.12

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over