rs10503640

Positions:

• chr8-18881817-A-G
• chr8-18881817-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.131-9084T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,190 control chromosomes in the GnomAD database, including 2,261 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 0.17 (2261 hom., cov: 33)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD3	NM_015310.4	c.131-9084T>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.131-9084T>C		intron_variant		1	NM_015310.4	ENSP00000324127	P3
PSD3	ENST00000523619.5	c.-66+5119T>C		intron_variant		1		ENSP00000430640	A2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26302 AN: 152072 Hom.: 2260 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.173 AC: 26314 AN: 152190 Hom.: 2261 Cov.: 33 AF XY: 0.175 AC XY: 13044 AN XY: 74402

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.170

Alfa AF: 0.120 Hom.: 259

Bravo AF: 0.175

Asia WGS AF: 0.239 AC: 830 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10503640; hg19: chr8-18739327;