Variant 10-102403252-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002779.5(PSD):c.3023G>C(p.Arg1008Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,606,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PSD
NM_002779.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0900

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09475458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD	NM_002779.5 linkuse as main transcript	c.3023G>C	p.Arg1008Pro	missense_variant	17/17	ENST00000020673.6	NP_002770.3	A5PKW4-1
PSD	NM_001270965.2 linkuse as main transcript	c.3023G>C	p.Arg1008Pro	missense_variant	18/18		NP_001257894.1	A5PKW4-1
PSD	NM_001270966.2 linkuse as main transcript	c.1886G>C	p.Arg629Pro	missense_variant	18/18		NP_001257895.1	A5PKW4-2Q86YI3
PSD	NR_073110.2 linkuse as main transcript	n.1315G>C		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PSD	ENST00000020673.6 linkuse as main transcript	c.3023G>C	p.Arg1008Pro	missense_variant	17/17	1	NM_002779.5	ENSP00000020673.5	A5PKW4-1
PSD	ENST00000406432.5 linkuse as main transcript	c.3023G>C	p.Arg1008Pro	missense_variant	18/18	1		ENSP00000384830.1	A5PKW4-1
PSD	ENST00000611678.4 linkuse as main transcript	c.1886G>C	p.Arg629Pro	missense_variant	18/18	1		ENSP00000481250.1	A5PKW4-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1454224

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000678

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

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

Jan 17, 2024

The c.3023G>C (p.R1008P) alteration is located in exon 17 (coding exon 16) of the PSD gene. This alteration results from a G to C substitution at nucleotide position 3023, causing the arginine (R) at amino acid position 1008 to be replaced by a proline (P). 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

0.090

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

.;T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.75

T;T;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.095

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;M;M

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-4.4

.;D;D

REVEL

Benign

0.029

Sift

Uncertain

0.0080

.;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.43

B;B;B

Vest4

0.14

MutPred

0.43

.;Loss of MoRF binding (P = 0.0011);Loss of MoRF binding (P = 0.0011);

MVP

0.10

MPC

0.070

ClinPred

0.91

GERP RS

3.3

Varity_R

0.57

gMVP

0.40

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