chr8-18572586-C-G

Variant names:

• chr8-18572586-C-G
• rs1802210420
• NM_015310.4:c.2726G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015310.4(PSD3):​c.2726G>C​(p.Gly909Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G909D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PSD3 NM_015310.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

PSD3 (HGNC:19093): (pleckstrin and Sec7 domain containing 3) Predicted to enable guanyl-nucleotide exchange factor activity and phospholipid binding activity. Predicted to be involved in regulation of ARF protein signal transduction and regulation of catalytic activity. Predicted to be located in membrane. Predicted to be active in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

PSD3 Gene-Disease associations (from GenCC):

• antecubital pterygium syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.764

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.2726G>C	p.Gly909Ala	missense_variant	Exon 14 of 16	ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.2726G>C	p.Gly909Ala	missense_variant	Exon 14 of 16	1	NM_015310.4	ENSP00000324127.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	.;T;.;T;.
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.76	D;D;D;D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Pathogenic	3.1	.;M;.;.;.
PhyloP100		7.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.3	D;.;D;D;D
REVEL	Pathogenic	0.73
Sift	Benign	0.055	T;.;D;D;T
Sift4G	Uncertain	0.025	D;D;D;D;D
Polyphen		0.99, 0.99, 0.67	.;D;D;P;.
Vest4		0.76
MutPred		0.49		.;Loss of catalytic residue at P906 (P = 0.1205);.;.;.;
MVP		0.83
MPC		0.17
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.15
gMVP		0.51
Mutation Taster		=31/69	disease causing

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

Other links and lift over

dbSNP: rs1802210420; hg19: chr8-18430096;