Variant chr10-102403360-G-A 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.2915C>T(p.Ala972Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,834 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PSD
NM_002779.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.140

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 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=0.043413073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD	NM_002779.5 linkuse as main transcript	c.2915C>T	p.Ala972Val	missense_variant	17/17	ENST00000020673.6	NP_002770.3	A5PKW4-1
PSD	NM_001270965.2 linkuse as main transcript	c.2915C>T	p.Ala972Val	missense_variant	18/18		NP_001257894.1	A5PKW4-1
PSD	NM_001270966.2 linkuse as main transcript	c.1778C>T	p.Ala593Val	missense_variant	18/18		NP_001257895.1	A5PKW4-2Q86YI3
PSD	NR_073110.2 linkuse as main transcript	n.1207C>T		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.2915C>T	p.Ala972Val	missense_variant	17/17	1	NM_002779.5	ENSP00000020673.5	A5PKW4-1
PSD	ENST00000406432.5 linkuse as main transcript	c.2915C>T	p.Ala972Val	missense_variant	18/18	1		ENSP00000384830.1	A5PKW4-1
PSD	ENST00000611678.4 linkuse as main transcript	c.1778C>T	p.Ala593Val	missense_variant	18/18	1		ENSP00000481250.1	A5PKW4-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250732

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135620

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461632

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727146

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

ExAC

AF:

0.0000165

AC:

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 24, 2024

The c.2915C>T (p.A972V) alteration is located in exon 17 (coding exon 16) of the PSD gene. This alteration results from a C to T substitution at nucleotide position 2915, causing the alanine (A) at amino acid position 972 to be replaced by a valine (V). 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

0.094

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.94

DANN

Uncertain

0.98

DEOGEN2

Benign

0.046

.;T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.16

T;T;.

M_CAP

Benign

0.0090

MetaRNN

Benign

0.043

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

.;N;N

REVEL

Benign

0.014

Sift

Benign

0.080

.;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.056

MutPred

0.28

.;Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);

MVP

0.13

MPC

0.048

ClinPred

0.098

GERP RS

2.8

Varity_R

0.025

gMVP

0.14

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