chr8-18672254-T-C

Position:

• chr8-18672254-T-C

Variant summary

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

The NM_015310.4(PSD3):​c.2173-16569A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 152,114 control chromosomes in the GnomAD database, including 166 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 0.024 (166 hom., cov: 32)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.665

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD3	NM_015310.4	c.2173-16569A>G		intron_variant		ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.2173-16569A>G		intron_variant		1	NM_015310.4	ENSP00000324127.8

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3601 AN: 151996 Hom.: 163 Cov.: 32

Gnomad AFR AF: 0.00471

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0792

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.0272

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

GnomAD4 genome AF: 0.0237 AC: 3610 AN: 152114 Hom.: 166 Cov.: 32 AF XY: 0.0269 AC XY: 1999 AN XY: 74358

Gnomad4 AFR AF: 0.00470

Gnomad4 AMR AF: 0.0799

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0365

Gnomad4 NFE AF: 0.0119

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.00710 Hom.: 3

Bravo AF: 0.0271

Asia WGS AF: 0.0650 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.0
DANN	Benign	0.70

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: rs17695724; hg19: chr8-18529764;