Variant chr10-102403972-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002779.5(PSD):c.2714G>A(p.Arg905Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,559,544 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 9 hom. )

Consequence

PSD
NM_002779.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.41

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052475333).

BP6

Variant 10-102403972-C-T is Benign according to our data. Variant chr10-102403972-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 770767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD	NM_002779.5 linkuse as main transcript	c.2714G>A	p.Arg905Gln	missense_variant	16/17	ENST00000020673.6	NP_002770.3	A5PKW4-1
PSD	NM_001270965.2 linkuse as main transcript	c.2714G>A	p.Arg905Gln	missense_variant	17/18		NP_001257894.1	A5PKW4-1
PSD	NM_001270966.2 linkuse as main transcript	c.1577G>A	p.Arg526Gln	missense_variant	17/18		NP_001257895.1	A5PKW4-2Q86YI3
PSD	NR_073110.2 linkuse as main transcript	n.1006G>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.2714G>A	p.Arg905Gln	missense_variant	16/17	1	NM_002779.5	ENSP00000020673.5	A5PKW4-1
PSD	ENST00000406432.5 linkuse as main transcript	c.2714G>A	p.Arg905Gln	missense_variant	17/18	1		ENSP00000384830.1	A5PKW4-1
PSD	ENST00000611678.4 linkuse as main transcript	c.1577G>A	p.Arg526Gln	missense_variant	17/18	1		ENSP00000481250.1	A5PKW4-2

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

314

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00321

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00162

AC:

271

AN:

167640

Hom.:

AF XY:

0.00154

AC XY:

138

AN XY:

89664

show subpopulations

Gnomad AFR exome

AF:

0.000497

Gnomad AMR exome

AF:

0.000803

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00164

Gnomad NFE exome

AF:

0.00316

Gnomad OTH exome

AF:

0.00129

GnomAD4 exome

AF:

0.00268

AC:

3772

AN:

1407278

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

1768

AN XY:

695986

show subpopulations

Gnomad4 AFR exome

AF:

0.000495

Gnomad4 AMR exome

AF:

0.000721

Gnomad4 ASJ exome

AF:

0.0000396

Gnomad4 EAS exome

AF:

0.0000271

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00197

Gnomad4 NFE exome

AF:

0.00325

Gnomad4 OTH exome

AF:

0.00180

GnomAD4 genome

AF:

0.00206

AC:

314

AN:

152266

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00321

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.00205

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000916

AC:

ESP6500EA

AF:

0.00292

AC:

ExAC

AF:

0.00169

AC:

199

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.081

.;T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.059

LIST_S2

Uncertain

0.91

D;D;.

M_CAP

Benign

0.0094

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

.;L;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.3

.;N;N

REVEL

Benign

0.031

Sift

Benign

0.12

.;T;T

Sift4G

Benign

0.22

T;D;D

Polyphen

0.35

B;B;B

Vest4

0.29

MVP

0.15

MPC

0.24

ClinPred

0.018

GERP RS

2.4

Varity_R

0.098

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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