8-18708295-A-G

Position:

• chr8-18708295-A-G

Variant summary

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

The ENST00000327040.13(PSD3):​c.2173-52610T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,086 control chromosomes in the GnomAD database, including 46,762 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 0.75 (46762 hom., cov: 32)
• Consequence: PSD3 ENST00000327040.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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 (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD3	NM_015310.4	c.2173-52610T>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.2173-52610T>C		intron_variant		1	NM_015310.4	ENSP00000324127	P3
PSD3	ENST00000286485.12	c.571-52610T>C		intron_variant		1		ENSP00000286485	A1
PSD3	ENST00000523619.5	c.1978-52610T>C		intron_variant		1		ENSP00000430640	A2
PSD3	ENST00000518315.5	c.*179-52610T>C		intron_variant, NMD_transcript_variant		2		ENSP00000428889

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113832 AN: 151968 Hom.: 46762 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.749 AC: 113846 AN: 152086 Hom.: 46762 Cov.: 32 AF XY: 0.745 AC XY: 55406 AN XY: 74366

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.935

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.900

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.780

Alfa AF: 0.897 Hom.: 76704

Bravo AF: 0.720

Asia WGS AF: 0.654 AC: 2273 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.56

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: rs901729; hg19: chr8-18565805;