8-18806784-C-G

Variant names:

• chr8-18806784-C-G
• rs1386688
• NM_015310.4:c.1635-1886G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015310.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSD3	NM_015310.4	MANE Select	c.1635-1886G>C		intron	N/A	NP_056125.3
	PSD3	NM_001412866.1		c.1938-1886G>C		intron	N/A	NP_001399795.1
	PSD3	NM_001412865.1		c.1938-1886G>C		intron	N/A	NP_001399794.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSD3	ENST00000327040.13	TSL:1 MANE Select	c.1635-1886G>C		intron	N/A	ENSP00000324127.8	Q9NYI0-2
	PSD3	ENST00000523619.5	TSL:1	c.1440-1886G>C		intron	N/A	ENSP00000430640.1	E5RJ29
	PSD3	ENST00000286485.12	TSL:1	c.33-1886G>C		intron	N/A	ENSP00000286485.8	Q9NYI0-3

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

African (AFR) AF: 0.529 AC: 21938 AN: 41438

American (AMR) AF: 0.224 AC: 3424 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 595 AN: 3470

East Asian (EAS) AF: 0.321 AC: 1658 AN: 5164

South Asian (SAS) AF: 0.180 AC: 869 AN: 4822

European-Finnish (FIN) AF: 0.261 AC: 2755 AN: 10564

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11581 AN: 67976

Other (OTH) AF: 0.258 AC: 544 AN: 2108

Alfa AF: 0.101 Hom.: 145

Bravo AF: 0.298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.052
DANN	Benign	0.42
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1386688; hg19: chr8-18664294;