rs7015570

Positions:

• chr8-18662569-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015310.4(PSD3):​c.2173-6884T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,132 control chromosomes in the GnomAD database, including 8,854 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 (8854 hom., cov: 33)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD3	NM_015310.4	c.2173-6884T>C		intron_variant		ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.2173-6884T>C		intron_variant		1	NM_015310.4	ENSP00000324127	P3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43865 AN: 152014 Hom.: 8813 Cov.: 33

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.289 AC: 43961 AN: 152132 Hom.: 8854 Cov.: 33 AF XY: 0.296 AC XY: 22030 AN XY: 74384

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.258

Alfa AF: 0.181 Hom.: 4365

Bravo AF: 0.309

Asia WGS AF: 0.529 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.62

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: rs7015570; hg19: chr8-18520079;