8-18723697-C-T

Variant names:

• chr8-18723697-C-T
• rs1386687
• NM_015310.4:c.2172+41752G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015310.4(PSD3):​c.2172+41752G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 152,296 control chromosomes in the GnomAD database, including 65,969 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 0.93 (65969 hom., cov: 33)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433
• Publications: 7 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

ENSG00000187229 (HGNC:58211):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.2172+41752G>A		intron_variant	Intron 9 of 15	ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.2172+41752G>A		intron_variant	Intron 9 of 15	1	NM_015310.4	ENSP00000324127.8

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141566 AN: 152178 Hom.: 65932 Cov.: 33

Gnomad AFR AF: 0.952

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.928

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

GnomAD4 genome AF: 0.930 AC: 141663 AN: 152296 Hom.: 65969 Cov.: 33 AF XY: 0.926 AC XY: 68933 AN XY: 74450

African (AFR) AF: 0.952 AC: 39568 AN: 41580

American (AMR) AF: 0.862 AC: 13185 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3142 AN: 3472

East Asian (EAS) AF: 0.818 AC: 4224 AN: 5164

South Asian (SAS) AF: 0.871 AC: 4200 AN: 4822

European-Finnish (FIN) AF: 0.949 AC: 10073 AN: 10612

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.943 AC: 64179 AN: 68030

Other (OTH) AF: 0.929 AC: 1966 AN: 2116

Alfa AF: 0.930 Hom.: 26886

Bravo AF: 0.923

Asia WGS AF: 0.872 AC: 3035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.49
PhyloP100		-0.43
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: rs1386687; hg19: chr8-18581207;