8-18811830-C-T

Variant names:

• chr8-18811830-C-T
• rs2638658
• NM_015310.4:c.1635-6932G>A

Variant summary

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

The NM_015310.4(PSD3):​c.1635-6932G>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
• 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 (NFE) allele frequency at 95% confidence interval = 0.642 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.1635-6932G>A		intron	N/A	NP_056125.3
	PSD3	NM_001412866.1		c.1938-6932G>A		intron	N/A	NP_001399795.1
	PSD3	NM_001412865.1		c.1938-6932G>A		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.1635-6932G>A		intron	N/A	ENSP00000324127.8	Q9NYI0-2
	PSD3	ENST00000523619.5	TSL:1	c.1440-6932G>A		intron	N/A	ENSP00000430640.1	E5RJ29
	PSD3	ENST00000519851.5	TSL:5	c.-43-6932G>A		intron	N/A	ENSP00000429069.1	E5RJE4

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

African (AFR) AF: 0.253 AC: 10482 AN: 41430

American (AMR) AF: 0.541 AC: 8242 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2196 AN: 3468

East Asian (EAS) AF: 0.315 AC: 1622 AN: 5154

South Asian (SAS) AF: 0.517 AC: 2487 AN: 4814

European-Finnish (FIN) AF: 0.602 AC: 6328 AN: 10520

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43948 AN: 67952

Other (OTH) AF: 0.541 AC: 1142 AN: 2110

Alfa AF: 0.510 Hom.: 3885

Bravo AF: 0.492

Asia WGS AF: 0.425 AC: 1479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.49
DANN	Benign	0.30
PhyloP100		0.087
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2638658; hg19: chr8-18669340;