rs1386688

Positions:

• chr8-18806784-C-G
• chr8-18806784-C-T

Variant summary

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

The NM_015310.4(PSD3):​c.1635-1886G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,026 control chromosomes in the GnomAD database, including 8,114 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 0.29 (8114 hom., cov: 33)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD3	NM_015310.4	c.1635-1886G>C		intron_variant		ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.1635-1886G>C		intron_variant		1	NM_015310.4	ENSP00000324127.8

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43591 AN: 151908 Hom.: 8101 Cov.: 33

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.287 AC: 43646 AN: 152026 Hom.: 8114 Cov.: 33 AF XY: 0.290 AC XY: 21523 AN XY: 74342

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.258

Alfa AF: 0.101 Hom.: 145

Bravo AF: 0.298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.052
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1386688; hg19: chr8-18664294;