8-18870439-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015310.4(PSD3):c.1238+1187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,992 control chromosomes in the GnomAD database, including 3,833 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3833 hom., cov: 31)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSD3	NM_015310.4	c.1238+1187T>C		intron_variant		ENST00000327040.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSD3	ENST00000327040.13	c.1238+1187T>C		intron_variant		1	NM_015310.4	P3
PSD3	ENST00000523619.5	c.1043+1187T>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32927 AN: 151874 Hom.: 3825 Cov.: 31

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.217 AC: 32968 AN: 151992 Hom.: 3833 Cov.: 31 AF XY: 0.220 AC XY: 16373 AN XY: 74288

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.212

Alfa AF: 0.130 Hom.: 296

Bravo AF: 0.223

Asia WGS AF: 0.299 AC: 1038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	5.8
Dann	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3758141; hg19: chr8-18727949;