8-18530531-C-T

Position:

• chr8-18530531-C-T

Variant summary

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

The NM_015310.4(PSD3):​c.*5212G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,518 control chromosomes in the GnomAD database, including 45,962 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 0.76 (45804 hom., cov: 32)
  • Exomes 𝑓: 0.87 (158 hom.)
• Consequence: PSD3 NM_015310.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSD3	NM_015310.4	c.*5212G>A		3_prime_UTR_variant	16/16	ENST00000327040.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSD3	ENST00000327040.13	c.*5212G>A		3_prime_UTR_variant	16/16	1	NM_015310.4	P3

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115164 AN: 151974 Hom.: 45793 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.796

GnomAD4 exome AF: 0.869 AC: 370 AN: 426 Hom.: 158 Cov.: 0 AF XY: 0.867 AC XY: 222 AN XY: 256

Gnomad4 FIN exome AF: 0.869

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.757 AC: 115194 AN: 152092 Hom.: 45804 Cov.: 32 AF XY: 0.760 AC XY: 56557 AN XY: 74392

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.899

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.796

Alfa AF: 0.843 Hom.: 73569

Bravo AF: 0.748

Asia WGS AF: 0.776 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.2
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3739396; hg19: chr8-18388041;