Variant 2-113182485-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012455.3(PSD4):c.29A>G(p.His10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,612,364 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 5 hom. )

Consequence

PSD4
NM_012455.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.69

Variant links:

Genes affected

PSD4 (HGNC:19096): (pleckstrin and Sec7 domain containing 4) 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. Located in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

PSD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055424273).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSD4	NM_012455.3 linkuse as main transcript	c.29A>G	p.His10Arg	missense_variant	2/17	ENST00000245796.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSD4	ENST00000245796.11 linkuse as main transcript	c.29A>G	p.His10Arg	missense_variant	2/17	1	NM_012455.3	P3	Q8NDX1-1

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

230

AN:

151782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000474

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00250

Gnomad OTH

AF:

0.00433

GnomAD3 exomes

AF:

0.00131

AC:

328

AN:

249868

Hom.:

AF XY:

0.00142

AC XY:

192

AN XY:

134996

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.000930

Gnomad ASJ exome

AF:

0.00211

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000881

Gnomad NFE exome

AF:

0.00208

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00223

AC:

3252

AN:

1460464

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1534

AN XY:

726416

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00227

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000768

Gnomad4 NFE exome

AF:

0.00263

Gnomad4 OTH exome

AF:

0.00230

GnomAD4 genome

AF:

0.00151

AC:

230

AN:

151900

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

100

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.000483

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000474

Gnomad4 NFE

AF:

0.00250

Gnomad4 OTH

AF:

0.00428

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00158

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00127

AC:

154

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00213

EpiControl

AF:

0.00237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.29A>G (p.H10R) alteration is located in exon 2 (coding exon 1) of the PSD4 gene. This alteration results from a A to G substitution at nucleotide position 29, causing the histidine (H) at amino acid position 10 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.048

Sift

Uncertain

0.0070

D;D

Sift4G

Benign

0.71

T;T

Polyphen

0.0050

B;B

Vest4

0.31

MVP

0.24

MPC

0.13

ClinPred

0.026

GERP RS

2.5

Varity_R

0.13

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over