8-18616077-T-C

Variant names:

• chr8-18616077-T-C
• rs10106755
• NM_015310.4:c.2411-15643A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

PSD3 Gene-Disease associations (from GenCC):

• antecubital pterygium syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

LOC124901896 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015310.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSD3	NM_015310.4	MANE Select	c.2411-15643A>G		intron	N/A	NP_056125.3
	PSD3	NM_001412866.1		c.2795-15643A>G		intron	N/A	NP_001399795.1
	PSD3	NM_001412865.1		c.2714-15643A>G		intron	N/A	NP_001399794.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSD3	ENST00000327040.13	TSL:1 MANE Select	c.2411-15643A>G		intron	N/A	ENSP00000324127.8
	PSD3	ENST00000523619.5	TSL:1	c.2216-15643A>G		intron	N/A	ENSP00000430640.1
	PSD3	ENST00000286485.12	TSL:1	c.809-15643A>G		intron	N/A	ENSP00000286485.8

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

African (AFR) AF: 0.688 AC: 28547 AN: 41494

American (AMR) AF: 0.580 AC: 8877 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2403 AN: 3470

East Asian (EAS) AF: 0.510 AC: 2623 AN: 5144

South Asian (SAS) AF: 0.594 AC: 2869 AN: 4828

European-Finnish (FIN) AF: 0.514 AC: 5437 AN: 10574

Middle Eastern (MID) AF: 0.784 AC: 229 AN: 292

European-Non Finnish (NFE) AF: 0.647 AC: 43963 AN: 67996

Other (OTH) AF: 0.639 AC: 1347 AN: 2108

Alfa AF: 0.650 Hom.: 23505

Bravo AF: 0.644

Asia WGS AF: 0.590 AC: 2054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.69
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10106755; hg19: chr8-18473587;