8-18741087-G-A

Position:

• chr8-18741087-G-A

Variant summary

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

The NM_015310.4(PSD3):​c.2172+24362C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,234 control chromosomes in the GnomAD database, including 1,120 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 0.091 (1120 hom., cov: 32)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSD3	NM_015310.4	c.2172+24362C>T		intron_variant		ENST00000327040.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSD3	ENST00000327040.13	c.2172+24362C>T		intron_variant		1	NM_015310.4	P3
PSD3	ENST00000286485.12	c.570+24362C>T		intron_variant		1		A1
PSD3	ENST00000523619.5	c.1977+24362C>T		intron_variant		1		A2
PSD3	ENST00000518315.5	c.*178+24362C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13890 AN: 152116 Hom.: 1115 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0928

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

GnomAD4 genome AF: 0.0914 AC: 13909 AN: 152234 Hom.: 1120 Cov.: 32 AF XY: 0.0941 AC XY: 7005 AN XY: 74438

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.0444

Gnomad4 OTH AF: 0.0961

Alfa AF: 0.0590 Hom.: 560

Bravo AF: 0.102

Asia WGS AF: 0.255 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.51
DANN	Benign	0.21

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: rs10096702; hg19: chr8-18598597;