8-18811830-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.1635-6932G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,886 control chromosomes in the GnomAD database, including 21,977 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 0.51 (21977 hom., cov: 31)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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 (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSD3	NM_015310.4	c.1635-6932G>A		intron_variant		ENST00000327040.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSD3	ENST00000327040.13	c.1635-6932G>A		intron_variant		1	NM_015310.4	P3
PSD3	ENST00000523619.5	c.1440-6932G>A		intron_variant		1		A2
PSD3	ENST00000519851.5	c.-43-6932G>A		intron_variant		5
PSD3	ENST00000518303.5	n.240-6932G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77213 AN: 151768 Hom.: 21963 Cov.: 31

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.509 AC: 77241 AN: 151886 Hom.: 21977 Cov.: 31 AF XY: 0.505 AC XY: 37475 AN XY: 74214

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.541

Alfa AF: 0.517 Hom.: 3849

Bravo AF: 0.492

Asia WGS AF: 0.425 AC: 1479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.49
Dann	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2638658; hg19: chr8-18669340;