8-18616077-T-C

Position:

• chr8-18616077-T-C

Variant summary

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

The NM_015310.4(PSD3):​c.2411-15643A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,116 control chromosomes in the GnomAD database, including 31,075 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 0.64 (31075 hom., cov: 33)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619

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]

LOC124901896 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD3	NM_015310.4	c.2411-15643A>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.2411-15643A>G		intron_variant		1	NM_015310.4	ENSP00000324127.8

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96771 AN: 151998 Hom.: 31037 Cov.: 33

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.637 AC: 96859 AN: 152116 Hom.: 31075 Cov.: 33 AF XY: 0.629 AC XY: 46727 AN XY: 74338

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.639

Alfa AF: 0.643 Hom.: 18387

Bravo AF: 0.644

Asia WGS AF: 0.590 AC: 2054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.69

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: rs10106755; hg19: chr8-18473587;