8-19065067-G-C

Variant names:

• chr8-19065067-G-C
• rs2410601
• NM_001412866.1:c.324+19139C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001412866.1(PSD3):​c.324+19139C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,898 control chromosomes in the GnomAD database, including 21,051 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 0.52 (21051 hom., cov: 31)
• Consequence: PSD3 NM_001412866.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001412866.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSD3	NM_001412866.1		c.324+19139C>G		intron	N/A	NP_001399795.1
	PSD3	NM_001412865.1		c.324+19139C>G		intron	N/A	NP_001399794.1
	PSD3	NM_001412868.1		c.324+19139C>G		intron	N/A	NP_001399797.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSD3	ENST00000521475.1	TSL:2	c.324+19139C>G		intron	N/A	ENSP00000428405.1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78453 AN: 151780 Hom.: 21034 Cov.: 31

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.517 AC: 78516 AN: 151898 Hom.: 21051 Cov.: 31 AF XY: 0.521 AC XY: 38688 AN XY: 74244

African (AFR) AF: 0.405 AC: 16771 AN: 41400

American (AMR) AF: 0.615 AC: 9382 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1681 AN: 3464

East Asian (EAS) AF: 0.857 AC: 4420 AN: 5160

South Asian (SAS) AF: 0.472 AC: 2266 AN: 4804

European-Finnish (FIN) AF: 0.603 AC: 6351 AN: 10538

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35890 AN: 67958

Other (OTH) AF: 0.526 AC: 1111 AN: 2112

Alfa AF: 0.504 Hom.: 2419

Bravo AF: 0.517

Asia WGS AF: 0.648 AC: 2254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.39
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs2410601; hg19: chr8-18922577;