8-18871228-C-G

Position:

• chr8-18871228-C-G

Variant summary

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

The NM_015310.4(PSD3):​c.1238+398G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,122 control chromosomes in the GnomAD database, including 2,048 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 0.15 (2048 hom., cov: 32)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD3	NM_015310.4	c.1238+398G>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.1238+398G>C		intron_variant		1	NM_015310.4	ENSP00000324127	P3
PSD3	ENST00000523619.5	c.1043+398G>C		intron_variant		1		ENSP00000430640	A2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23314 AN: 152004 Hom.: 2043 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.153 AC: 23342 AN: 152122 Hom.: 2048 Cov.: 32 AF XY: 0.158 AC XY: 11732 AN XY: 74340

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.154

Alfa AF: 0.132 Hom.: 181

Bravo AF: 0.155

Asia WGS AF: 0.267 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6998537; hg19: chr8-18728738;