rs2035681

Positions:

• chr8-18592131-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	Protein	UniProt
PSD3	NM_015310.4	c.2481+8233C>T		intron_variant		ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.2481+8233C>T		intron_variant		1	NM_015310.4	ENSP00000324127	P3

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

Gnomad4 AFR AF: 0.0538

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.233

Alfa AF: 0.251 Hom.: 2395

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2035681; hg19: chr8-18449641;