10-102403861-T-C

Position:

• chr10-102403861-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002779.5(PSD):​c.2825A>G​(p.Glu942Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PSD NM_002779.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.78

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD	NM_002779.5	c.2825A>G	p.Glu942Gly	missense_variant	16/17	ENST00000020673.6	NP_002770.3
PSD	NM_001270965.2	c.2825A>G	p.Glu942Gly	missense_variant	17/18		NP_001257894.1
PSD	NM_001270966.2	c.1688A>G	p.Glu563Gly	missense_variant	17/18		NP_001257895.1
PSD	NR_073110.2	n.1117A>G		non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSD	ENST00000020673.6	c.2825A>G	p.Glu942Gly	missense_variant	16/17	1	NM_002779.5	ENSP00000020673.5
PSD	ENST00000406432.5	c.2825A>G	p.Glu942Gly	missense_variant	17/18	1		ENSP00000384830.1
PSD	ENST00000611678.4	c.1688A>G	p.Glu563Gly	missense_variant	17/18	1		ENSP00000481250.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

The c.2825A>G (p.E942G) alteration is located in exon 16 (coding exon 15) of the PSD gene. This alteration results from a A to G substitution at nucleotide position 2825, causing the glutamic acid (E) at amino acid position 942 to be replaced by a glycine (G). 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	0.26
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.96	D;D;.
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.0	.;M;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.1	.;D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	.;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.98	D;D;D
Vest4		0.66
MutPred		0.31		.;Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);
MVP		0.26
MPC		0.35
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.63
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-104163618;