rs2632841

Positions:

• chr8-18814273-A-C
• chr8-18814273-A-T

Variant summary

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

The NM_015310.4(PSD3):​c.1635-9375T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 152,098 control chromosomes in the GnomAD database, including 19,731 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 0.47 (19731 hom., cov: 32)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD3	NM_015310.4	c.1635-9375T>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.1635-9375T>G		intron_variant		1	NM_015310.4	ENSP00000324127	P3
PSD3	ENST00000523619.5	c.1440-9375T>G		intron_variant		1		ENSP00000430640	A2
PSD3	ENST00000519851.5	c.-43-9375T>G		intron_variant		5		ENSP00000429069
PSD3	ENST00000518303.5	n.240-9375T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71988 AN: 151982 Hom.: 19721 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.473 AC: 72011 AN: 152098 Hom.: 19731 Cov.: 32 AF XY: 0.480 AC XY: 35671 AN XY: 74364

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.494

Alfa AF: 0.550 Hom.: 26883

Bravo AF: 0.457

Asia WGS AF: 0.635 AC: 2207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.8
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2632841; hg19: chr8-18671783;