rs2035681

Variant names:

• chr8-18592131-G-A
• rs2035681
• NM_015310.4:c.2481+8233C>T

Variant summary

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

The NM_015310.4(PSD3):​c.2481+8233C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,010 control chromosomes in the GnomAD database, including 3,797 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 0.20 (3797 hom., cov: 32)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• 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: 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.2481+8233C>T		intron_variant	Intron 12 of 15	ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.2481+8233C>T		intron_variant	Intron 12 of 15	1	NM_015310.4	ENSP00000324127.8

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30696 AN: 151892 Hom.: 3800 Cov.: 32

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.202 AC: 30699 AN: 152010 Hom.: 3797 Cov.: 32 AF XY: 0.199 AC XY: 14797 AN XY: 74300

African (AFR) AF: 0.0538 AC: 2234 AN: 41488

American (AMR) AF: 0.232 AC: 3531 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1068 AN: 5168

South Asian (SAS) AF: 0.149 AC: 720 AN: 4824

European-Finnish (FIN) AF: 0.237 AC: 2501 AN: 10536

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.280 AC: 18998 AN: 67966

Other (OTH) AF: 0.233 AC: 492 AN: 2112

Alfa AF: 0.252 Hom.: 2653

Bravo AF: 0.195

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.74
PhyloP100		0.042
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2035681; hg19: chr8-18449641;