Variant 10-102403930-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002779.5(PSD):c.2756G>A(p.Arg919Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000592 in 1,589,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

PSD
NM_002779.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

Variant links:

Genes affected

PSD (HGNC:9507): (pleckstrin and Sec7 domain containing) This gene encodes a Plekstrin homology and SEC7 domains-containing protein that functions as a guanine nucleotide exchange factor. The encoded protein regulates signal transduction by activating ADP-ribosylation factor 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

PSD links:

PSD (HGNC:):

PSD links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008870691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD	NM_002779.5 linkuse as main transcript	c.2756G>A	p.Arg919Gln	missense_variant	16/17	ENST00000020673.6	NP_002770.3	A5PKW4-1
PSD	NM_001270965.2 linkuse as main transcript	c.2756G>A	p.Arg919Gln	missense_variant	17/18		NP_001257894.1	A5PKW4-1
PSD	NM_001270966.2 linkuse as main transcript	c.1619G>A	p.Arg540Gln	missense_variant	17/18		NP_001257895.1	A5PKW4-2Q86YI3
PSD	NR_073110.2 linkuse as main transcript	n.1048G>A		non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PSD	ENST00000020673.6 linkuse as main transcript	c.2756G>A	p.Arg919Gln	missense_variant	16/17	1	NM_002779.5	ENSP00000020673.5	A5PKW4-1
PSD	ENST00000406432.5 linkuse as main transcript	c.2756G>A	p.Arg919Gln	missense_variant	17/18	1		ENSP00000384830.1	A5PKW4-1
PSD	ENST00000611678.4 linkuse as main transcript	c.1619G>A	p.Arg540Gln	missense_variant	17/18	1		ENSP00000481250.1	A5PKW4-2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000161

AC:

AN:

204378

Hom.:

AF XY:

0.000208

AC XY:

AN XY:

110324

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 SAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000585

AC:

AN:

1436742

Hom.:

Cov.:

AF XY:

0.0000828

AC XY:

AN XY:

712798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000842

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000109

Gnomad4 OTH exome

AF:

0.0000337

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000648

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Sep 03, 2024

The c.2756G>A (p.R919Q) alteration is located in exon 16 (coding exon 15) of the PSD gene. This alteration results from a G to A substitution at nucleotide position 2756, causing the arginine (R) at amino acid position 919 to be replaced by a glutamine (Q). 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

0.068

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

.;T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.37

T;T;.

M_CAP

Benign

0.015

MetaRNN

Benign

0.0089

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

.;L;L

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.49

.;N;N

REVEL

Benign

0.025

Sift

Benign

0.38

.;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.027

B;B;B

Vest4

0.19

MutPred

0.23

.;Loss of methylation at R919 (P = 0.0281);Loss of methylation at R919 (P = 0.0281);

MVP

0.14

MPC

0.27

ClinPred

0.12

GERP RS

4.3

Varity_R

0.053

gMVP

0.21

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