rs334206

Positions:

• chr8-19052608-G-A
• chr8-19052608-G-C

Variant summary

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

The NM_001412866.1(PSD3):​c.324+31598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,150 control chromosomes in the GnomAD database, including 7,173 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 0.28 (7173 hom., cov: 32)
• Consequence: PSD3 NM_001412866.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD3	NM_001412866.1	c.324+31598C>T		intron_variant			NP_001399795.1
PSD3	NM_001412865.1	c.324+31598C>T		intron_variant			NP_001399794.1
PSD3	NM_001412868.1	c.324+31598C>T		intron_variant			NP_001399797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000521475.1	c.324+31598C>T		intron_variant		2		ENSP00000428405.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42938 AN: 152032 Hom.: 7179 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.282 AC: 42943 AN: 152150 Hom.: 7173 Cov.: 32 AF XY: 0.281 AC XY: 20925 AN XY: 74372

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.279

Alfa AF: 0.319 Hom.: 1948

Bravo AF: 0.276

Asia WGS AF: 0.413 AC: 1438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs334206; hg19: chr8-18910118;